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Dr Stephen Man
Darllenydd
- ManS@caerdydd.ac.uk
- +44 29206 87056
- Adeilad Tenovus, Ystafell GF16, Ysbyty Athrofaol Cymru, Parc y Mynydd Bychan, Caerdydd, CF14 4XN
Trosolwyg
Rwy'n Ddarllenydd yn yr Adran Canser a Geneteg (DCG), yn yr Ysgol Meddygaeth. Mae fy ymchwil yn canolbwyntio ar rôl y system imiwnedd mewn canser. Rwy'n arbenigwr ar gelloedd T dynol ac am y pum mlynedd diwethaf, rwyf wedi bod yn astudio rôl y celloedd hyn mewn lewcemia. Mae fy ymchwil a ariannwyd gan Bloodwise ac Ymchwil Canser Cymru wedi nodi targedau newydd ar gyfer ymosodiad imiwnedd, ac wedi dangos bod gan gleifion â chlefyd mwy ymosodol boblogaethau celloedd T annormal. Ein nod yw trosi'r canfyddiadau hyn er budd cleifion.
Y tu allan i'r labordy, rwy'n weithgar mewn ymgysylltu â'r gymuned (manylion o dan y tab Ymgysylltu) ac roeddwn yn gyd-sylfaenydd Rhwydwaith Staff Rhyngwladol Prifysgol Caerdydd. Mae'r rhwydwaith hwn yn sefydliad staff gwirfoddol sy'n darparu cyngor a chefnogaeth i staff rhyngwladol wrth iddynt drosglwyddo i fywyd yng Nghaerdydd a'r DU. Cawsom ein cydnabod gan "Wobr Dathlu Rhagoriaeth Prifysgol Caerdydd am Gyfraniad Gwirfoddol" yn 2019.
Cyhoeddiad
2023
- Dolton, G. et al. 2023. Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy. Cell 186(16), pp. 3333-3349., article number: E27. (10.1016/j.cell.2023.06.020)
2021
- Man, S. et al. 2021. Synthetic peptides with inadvertent chemical modifications can activate potentially autoreactive T cells. The Journal of Immunology 207(4), pp. 1009-1017. (10.4049/jimmunol.2000756)
- Rastogi, N. et al. 2021. Use of an anti-CD200 blocking antibody improves immune responses to AML in vitro and in vivo. British Journal of Haematology 193(1), pp. 155-159. (10.1111/bjh.17125)
2020
- Elston, L. et al. 2020. Increased frequency of CD4+PD-1+HLA-DR+ T cells is associated with disease progression in CLL. British Journal of Haematology 188(6), pp. 872-880. (10.1111/bjh.16260)
2019
- Man, S. and Henley, P. 2019. Chronic lymphocytic leukaemia: the role of T cells in a B cell disease. British Journal of Haematology 186(2), pp. 220-233. (10.1111/bjh.15918)
2018
- Pirotte, E. F. et al. 2018. Sensitivity to inhibition of DNA repair by Olaparib in novel oropharyngeal cancer cell lines infected with Human Papillomavirus. PLoS ONE 13(12), pp. -., article number: e0207934. (10.1371/journal.pone.0207934)
2017
- Dockree, T. et al. 2017. CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold. Immunology and Cell Biology 95(1), pp. 68-76. (10.1038/icb.2016.85)
2016
- Parry, H. . M. et al. 2016. Cytomegalovirus infection does not impact on survival or time to first treatment in patients with Chronic Lymphocytic Leukaemia. American Journal of Hematology 91(8), pp. 776-781. (10.1002/ajh.24403)
- Sacco, J. J., Evans, M., Harrington, K. J., Man, S., Powell, N., Shaw, R. J. and Jones, T. M. 2016. Systemic listeriosis following vaccination with the attenuatedListeria monocytogenestherapeutic vaccine, ADXS11-001. Human Vaccines & Immunotherapeutics 12(4), pp. 1085-1086. (10.1080/21645515.2015.1121338)
2015
- Coles, S. J. et al. 2015. The immunosuppressive ligands PD-L1 and CD200 are linked in AML T-cell immunosuppression: identification of a new immunotherapeutic synapse. Leukemia 29, pp. 1952-1954. (10.1038/leu.2015.62)
- Reid, R., Redman, J. E., Rizkallah, P., Fegan, C. D., Pepper, C. J. and Man, S. T. 2015. CD8+ T-cell recognition of a synthetic epitope formed by t-butyl modification. Immunology 144(3), pp. 495-505. (10.1111/imm.12398)
2014
- Tristram, A. et al. 2014. Activity, safety, and feasibility of cidofovir and imiquimod for treatment of vulval intraepithelial neoplasia (RT³VIN): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncology 15(12), pp. 1361-1368. (10.1016/S1470-2045(14)70456-5)
- Stanton, R. J. et al. 2014. HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells. Cell Host and Microbe 16(2), pp. 201-214. (10.1016/j.chom.2014.07.005)
2013
- Wong, R. F., Pepper, C. J., Brennan, P., Nagorsen, D., Man, S. T. and Fegan, C. D. 2013. Blinatumomab induces autologous T cell killing of chronic lymphocytic leukemia cells. Haematologica 98(12), pp. 1930-1938. (10.3324/haematol.2012.082248)
- Al-Taei, S., Banner, R., Powell, N. G., Evans, M., Palaniappan, N., Tabi, Z. and Man, S. T. 2013. Decreased HPV-specific T cell responses and accumulation of immunosuppressive influences in oropharyngeal cancer patients following radical therapy. Cancer Immunology, Immunotherapy 62(12), pp. 1821-1830. (10.1007/s00262-013-1488-5)
- Man, S. 2013. Back to the future: learning from cancer vaccine trials in Cardiff. Applied Immunohistochemistry and Molecular Morphology 21(2), pp. 110-115. (10.1097/PAI.0b013e3182811612)
2012
- Coles, S., Hills, R. K., Wang, E. C. Y., Burnett, A. K., Man, S. T., Darley, R. L. and Tonks, A. 2012. Expression of CD200 on AML blasts directly suppresses memory T-cell function [Letter]. Leukemia 26(9), pp. 2148-2151. (10.1038/leu.2012.77)
- Coles, S., Hills, R. K., Wang, E. C. Y., Burnett, A. K., Man, S. T., Darley, R. L. and Tonks, A. 2012. Increased CD200 expression in acute myeloid leukemia is linked with an increased frequency of FoxP3+ regulatory T cells [Letter]. Leukemia 26(9), pp. 2146-2148. (10.1038/leu.2012.75)
- Nunes, C. T., Wong, R. F., Mason, M. D., Fegan, C. D., Man, S. T. and Pepper, C. J. 2012. Expansion of a CD8+PD-1+ replicative senescence phenotype in early stage CLL patients is associated with inverted CD4:CD8 ratios and disease progression. Clinical Cancer Research 18(3), pp. 678-687. (10.1158/1078-0432.CCR-11-2630)
2011
- Coles, S., Man, S. T., Hills, R. K., Wang, E. C. Y., Burnett, A. K., Darley, R. L. and Tonks, A. 2011. CD200 inhibits memory Th1 cell function in acute myeloid leukaemia (AML)[Abstract]. Immunology 135(S1), pp. 178. (10.1111/j.1365-2567.2011.03534.x)
- Nunes, C. T., Miners, K. L., Dolton, G. M., Pepper, C. J., Fegan, C. D., Mason, M. D. and Man, S. T. 2011. A novel tumor antigen derived from enhanced degradation of Bax protein in human cancers. Cancer Research 71(16), pp. 5435-5444. (10.1158/0008-5472.CAN-11-0393)
- Chan, P. K. S., Liu, S., Cheung, J. L. K., Cheung, T. H., Yeo, W., Chong, P. and Man, S. T. 2011. T-cell response to human papillomavirus type 52 L1, E6, and E7 peptides in women with transient infection, cervical intraepithelial neoplasia, and invasive cancer. Journal of Medical Virology 83(6), pp. 1023-1030. (10.1002/jmv.21889)
- Coles, S., Wang, E. C. Y., Man, S. T., Hills, R. K., Burnett, A. K., Tonks, A. and Darley, R. L. 2011. CD200 expression suppresses natural killer cell function and directly inhibits patient anti-tumor response in acute myeloid leukemia. Leukemia 25(5), pp. 792-799. (10.1038/leu.2011.1)
2010
- Campo, M. S. et al. 2010. HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells. Virology 407(1), pp. 137-142. (10.1016/j.virol.2010.07.044)
- Coles, S., Man, S. T., Hills, R. K., Wang, E. C. Y., Burnett, A. K., Darley, R. L. and Tonks, A. 2010. Over-expression of CD200 un acute myeloid leukemia mediates the expansion of regulatory T-lymphocytes and directly inhibits natural killer cell tumor immunity [Abstract]. Blood 116(21), pp. 218-218.
- Chan, P. K. S. et al. 2010. T-Cell response to human papillomavirus type 58 L1, E6, and E7 peptides in women with cleared infection, cervical intraepithelial neoplasia, or invasive cancer. Clinical and Vaccine Immunology 17(9), pp. 1315-1321. (10.1128/CVI.00105-10)
2008
- Thomas, K. J., Smith, K. L., Youde, S. J., Evans, M., Fiander, A. N., Borysiewicz, L. K. and Man, S. T. 2008. HPV16 E629-38-specific T cells kill cervical carcinoma cells despite partial evasion of T-cell effector function. International Journal of Cancer 122(12), pp. 2791-2799. (10.1002/ijc.23475)
- Tabi, Z. and Man, S. 2008. Cancer vaccines and immune monitoring (an overview). In: Hayat, M. A. ed. General methods and overviews, lung carcinoma and prostate carcinoma:. Methods of cancer diagnosis, therapy and prognosis Vol. 2. Springer, pp. 129-160., (10.1007/978-1-4020-8442-3)
2007
- Capper, R. et al. 2007. The nature of telomere fusion and a definition of the critical telomere length in human cells. Genes and Development 21(19), pp. 2495-2508. (10.1101/gad.439107)
2006
- McCarthy, C., Youde, S. J. and Man, S. T. 2006. Definition of an HPV18/45 cross-reactive human T-cell epitope after DNA immunisation of HLA-A2/KB transgenic mice. International Journal of Cancer 118(10), pp. 2514-21. (10.1002/ijc.21643)
- Fiander, A. N. et al. 2006. Prime-boost vaccination strategy in women with high-grade, noncervical anogenital intraepithelial neoplasia: clinical results from a multicenter phase II trial. International Journal of Gynecological Cancer 16(3), pp. 1075-1081. (10.1111/j.1525-1438.2006.00598.x)
2005
- Youde, S. J., McCarthy, C. M., Thomas, K. J., Smith, K. L. and Man, S. T. 2005. Cross-typic specificity and immunotherapeutic potential of a human HPV16 E7-specific CTL line. International Journal of Cancer 114(4), pp. 606-12. (10.1002/ijc.20779)
- Smith, K. L., Tristram, A. J., Gallagher, K. M., Fiander, A. N. and Man, S. T. 2005. Epitope specificity and longevity of a vaccine-induced human T cell response against HPV18. International Immunology 17(2), pp. 167-176. (10.1093/intimm/dxh197)
- Hill, S. C. et al. 2005. Activation of CD40 in cervical carcinoma cells facilitates CTL responses and augments chemotherapy-induced apoptosis. Journal of Immunology 174(1), pp. 41-50.
- Wall, S. R. et al. 2005. Cervical human papillomavirus infection and squamous intraepithelial lesions in rural Gambia, West Africa: viral sequence analysis and epidemiology. British Journal of Cancer 93(9), pp. 1068-1076. (10.1038/sj.bjc.6602736)
- Lyons, G. E., Roszkowski, J. J., Man, S. T., Yee, C., Kast, W. M. and Nishimura, M. I. 2005. T-cell receptor tetramer binding or the lack there of does not necessitate antigen reactivity in T-cell receptor transduced T cells. Cancer Immunology, Immunotherapy 55(9), pp. 1142-1150. (10.1007/s00262-005-0103-9)
2004
- Man, S. T., McMichael, A. J., Stauss, H. J. and Savage, P. 2004. Use of B cell-bound HLA-A2 class I monomers to generate high-avidity, allo-restricted CTLs against the leukemia-associated protein Wilms tumor antigen. Blood 103(12), pp. 4613-4615. (10.1182/blood-2003-11-3903)
- Smyth, L. J. C. et al. 2004. Immunological responses in women with human papillomavirus type 16 (HPV-16)-associated anogenital intraepithelial neoplasia induced by heterologous prime-boost HPV-16 oncogene vaccination. Clinical Cancer Research 10(9), pp. 2954-2961. (10.1158/1078-0432.CCR-03-0703)
2003
- Adams, M. et al. 2003. Dendritic cell (DC) based therapy for cervical cancer: use of DC pulsed with tumour lysate and matured with a novel synthetic clinically non-toxic double stranded RNA analogue poly [I]:poly [C(12)U] (Ampligen R). Vaccine 21(7-8), pp. 787-90. (10.1016/S0264-410X(02)00599-6)
- Fiander, A. N. and Man, S. T. 2003. Antiviral vaccination for treating intraepithelial neoplasia. In: Maclean, A. B., Singer, A. and Critchley, H. eds. Lower Genital Tract Neoplasia. London: RCOG Press, pp. 192-209.
2002
- Palmowski, M. J. et al. 2002. Competition between CTL narrows the immune response induced by prime-boost vaccination protocols. The Journal of Immunology 168(9), pp. 4391-4398. (10.4049/jimmunol.168.9.4391)
- Savage, P. et al. 2002. Induction of viral and tumour specific CTL responses using antibody targeted HLA class I peptide complexes. British Journal of Cancer 86(8), pp. 1336-1342. (10.1038/sj.bjc.6600223)
- Savage, P. et al. 2002. Anti-viral cytotoxic T cells inhibit the growth of cancer cells with antibody targeted hla class I/peptide complexes in scid mice. International Journal of Cancer 98(4), pp. 561-566. (10.1002/ijc.10219)
2001
- Evans, M. et al. 2001. Antigen processing defects in cervical carcinomas limit the presentation of a CTL epitope from human papillomavirus 16 E6. The Journal of Immunology 167(9), pp. 5420-5428.
- Man, S. T. and Fiander, A. N. 2001. Immunology of human papillomavirus infection in lower genital tract neoplasia [review]. Best Practice & Research Clinical Obstetrics & Gynaecology 15(5), pp. 701-714. (10.1053/beog.2001.0215)
- Adams, M. et al. 2001. Clinical studies of human papilloma vaccines in pre-invasive and invasive cancer. Vaccine 19(17-19), pp. 2549-2556. (10.1016/S0264-410X(00)00488-6)
- Adams, M. et al. 2001. Clinical studies of human papilloma vaccines in cervical cancer. In: Mackiewicz, A., Kurpisz, M. and Zeromski, J. eds. Progress in Basic and Clinical Immunology. Advances in Experimental Medicine and Biology Vol. 442. New York: Kluwer Academic/Plenum Publishers, pp. 419-427., (10.1007/978-1-4615-0685-0_61)
- Man, S. T. 2001. Recognition of human tumours: viral antigens as immunological targets for cytotoxic T cells. In: Robbins, R. A. and Rees, R. eds. Cancer Immunology. Immunology and Medicine Vol. 30. Springer, pp. 123-145.
- Lawson, T., Man, S. T., Williams, S., Boon, A. C. M., Zambon, M. and Borysiewicz, L. K. 2001. Influenza A antigen exposure selects dominant Vbeta17+ TCR in human CD8+ cytotoxic T cell responses. International Immunology 13(11), pp. 1373-1381. (10.1093/intimm/13.11.1373)
- Lawson, T. et al. 2001. Functional differences between influenza A-specific cytotoxic T lymphocyte clones expressing dominant and subdominant TCR. International Immunology 13(11), pp. 1383-1390. (10.1093/intimm/13.11.1383)
2000
- Youde, S. J., Dunbar, P. R. R., Evans, E. M. L., Fiander, A. N., Borysiewicz, L. K., Cerundolo, V. and Man, S. T. 2000. Use of fluorogenic histocompatibility leukocyte antigen-A*0201/HPV 16 E7 peptide complexes to isolate rare human cytotoxic T-lymphocyte-recognizing endogenous human papillomavirus antigens. Cancer Research 60(2), pp. 365-371.
- Evans, M., Man, S. T. and Borysiewicz, L. K. 2000. Vaccine strategies for cancer. In: Weissberg, P. ed. Horizons in Medicine., Vol. 12. London: Royal College of Physicians, pp. 289-300.
- Borysiewicz., L. K. and Man, S. T. 2000. Vaccinia-based human papillomavirus vaccines in cervical cancer. In: Stern, P. L., Beverley, P. C. L. and Carroll, M. W. eds. Cancer vaccines and immunotherapy. Cambridge, UK: Cambridge University Press, pp. 62-81.
1999
- Man, S. T., Evans, E. M. L., Nimako, M. and Borysiewicz, L. K. 1999. Recombinant vaccinia virus. In: Tindle, R. W. ed. Vaccines for Human Papillomavirus Infection and anogenital disease, 14th ed.. Medical Intelligence Unit Austin, Texas: R.G. Landes Company, pp. 69-90.
1997
- Nimako, M., Fiander, A. N., Wilkinson, G. W. G., Borysiewicz, L. K. and Man, S. T. 1997. Human papillomavirus-specific cytotoxic T lymphocytes in patients with cervical intraepithelial neoplasia grade III. Cancer Research 57(21), pp. 4855-4861.
- Fiander, A. N., Man, S. T., Borysiewicz, L. K. and Wilkinson, G. W. G. 1997. Therapeutic vaccines for cervical cancer: concept and clinical results. Biodrugs -Auckland- 8(5), pp. 331-338. (10.2165/00063030-199708050-00001)
1996
- Borysiewicz, L. K. et al. 1996. A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer. The Lancet 347(9014), pp. 1523-1527. (10.1016/s0140-6736(96)90674-1)
1995
- Borysiewicz, L. K. et al. 1995. Development and initial clinical studies of TA-HPV in cervical cancer. European Journal of Cancer 31(supp 3), pp. 17-17. (10.1016/0959-8049(95)99882-z)
Articles
- Dolton, G. et al. 2023. Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy. Cell 186(16), pp. 3333-3349., article number: E27. (10.1016/j.cell.2023.06.020)
- Man, S. et al. 2021. Synthetic peptides with inadvertent chemical modifications can activate potentially autoreactive T cells. The Journal of Immunology 207(4), pp. 1009-1017. (10.4049/jimmunol.2000756)
- Rastogi, N. et al. 2021. Use of an anti-CD200 blocking antibody improves immune responses to AML in vitro and in vivo. British Journal of Haematology 193(1), pp. 155-159. (10.1111/bjh.17125)
- Elston, L. et al. 2020. Increased frequency of CD4+PD-1+HLA-DR+ T cells is associated with disease progression in CLL. British Journal of Haematology 188(6), pp. 872-880. (10.1111/bjh.16260)
- Man, S. and Henley, P. 2019. Chronic lymphocytic leukaemia: the role of T cells in a B cell disease. British Journal of Haematology 186(2), pp. 220-233. (10.1111/bjh.15918)
- Pirotte, E. F. et al. 2018. Sensitivity to inhibition of DNA repair by Olaparib in novel oropharyngeal cancer cell lines infected with Human Papillomavirus. PLoS ONE 13(12), pp. -., article number: e0207934. (10.1371/journal.pone.0207934)
- Dockree, T. et al. 2017. CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold. Immunology and Cell Biology 95(1), pp. 68-76. (10.1038/icb.2016.85)
- Parry, H. . M. et al. 2016. Cytomegalovirus infection does not impact on survival or time to first treatment in patients with Chronic Lymphocytic Leukaemia. American Journal of Hematology 91(8), pp. 776-781. (10.1002/ajh.24403)
- Sacco, J. J., Evans, M., Harrington, K. J., Man, S., Powell, N., Shaw, R. J. and Jones, T. M. 2016. Systemic listeriosis following vaccination with the attenuatedListeria monocytogenestherapeutic vaccine, ADXS11-001. Human Vaccines & Immunotherapeutics 12(4), pp. 1085-1086. (10.1080/21645515.2015.1121338)
- Coles, S. J. et al. 2015. The immunosuppressive ligands PD-L1 and CD200 are linked in AML T-cell immunosuppression: identification of a new immunotherapeutic synapse. Leukemia 29, pp. 1952-1954. (10.1038/leu.2015.62)
- Reid, R., Redman, J. E., Rizkallah, P., Fegan, C. D., Pepper, C. J. and Man, S. T. 2015. CD8+ T-cell recognition of a synthetic epitope formed by t-butyl modification. Immunology 144(3), pp. 495-505. (10.1111/imm.12398)
- Tristram, A. et al. 2014. Activity, safety, and feasibility of cidofovir and imiquimod for treatment of vulval intraepithelial neoplasia (RT³VIN): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncology 15(12), pp. 1361-1368. (10.1016/S1470-2045(14)70456-5)
- Stanton, R. J. et al. 2014. HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells. Cell Host and Microbe 16(2), pp. 201-214. (10.1016/j.chom.2014.07.005)
- Wong, R. F., Pepper, C. J., Brennan, P., Nagorsen, D., Man, S. T. and Fegan, C. D. 2013. Blinatumomab induces autologous T cell killing of chronic lymphocytic leukemia cells. Haematologica 98(12), pp. 1930-1938. (10.3324/haematol.2012.082248)
- Al-Taei, S., Banner, R., Powell, N. G., Evans, M., Palaniappan, N., Tabi, Z. and Man, S. T. 2013. Decreased HPV-specific T cell responses and accumulation of immunosuppressive influences in oropharyngeal cancer patients following radical therapy. Cancer Immunology, Immunotherapy 62(12), pp. 1821-1830. (10.1007/s00262-013-1488-5)
- Man, S. 2013. Back to the future: learning from cancer vaccine trials in Cardiff. Applied Immunohistochemistry and Molecular Morphology 21(2), pp. 110-115. (10.1097/PAI.0b013e3182811612)
- Coles, S., Hills, R. K., Wang, E. C. Y., Burnett, A. K., Man, S. T., Darley, R. L. and Tonks, A. 2012. Expression of CD200 on AML blasts directly suppresses memory T-cell function [Letter]. Leukemia 26(9), pp. 2148-2151. (10.1038/leu.2012.77)
- Coles, S., Hills, R. K., Wang, E. C. Y., Burnett, A. K., Man, S. T., Darley, R. L. and Tonks, A. 2012. Increased CD200 expression in acute myeloid leukemia is linked with an increased frequency of FoxP3+ regulatory T cells [Letter]. Leukemia 26(9), pp. 2146-2148. (10.1038/leu.2012.75)
- Nunes, C. T., Wong, R. F., Mason, M. D., Fegan, C. D., Man, S. T. and Pepper, C. J. 2012. Expansion of a CD8+PD-1+ replicative senescence phenotype in early stage CLL patients is associated with inverted CD4:CD8 ratios and disease progression. Clinical Cancer Research 18(3), pp. 678-687. (10.1158/1078-0432.CCR-11-2630)
- Coles, S., Man, S. T., Hills, R. K., Wang, E. C. Y., Burnett, A. K., Darley, R. L. and Tonks, A. 2011. CD200 inhibits memory Th1 cell function in acute myeloid leukaemia (AML)[Abstract]. Immunology 135(S1), pp. 178. (10.1111/j.1365-2567.2011.03534.x)
- Nunes, C. T., Miners, K. L., Dolton, G. M., Pepper, C. J., Fegan, C. D., Mason, M. D. and Man, S. T. 2011. A novel tumor antigen derived from enhanced degradation of Bax protein in human cancers. Cancer Research 71(16), pp. 5435-5444. (10.1158/0008-5472.CAN-11-0393)
- Chan, P. K. S., Liu, S., Cheung, J. L. K., Cheung, T. H., Yeo, W., Chong, P. and Man, S. T. 2011. T-cell response to human papillomavirus type 52 L1, E6, and E7 peptides in women with transient infection, cervical intraepithelial neoplasia, and invasive cancer. Journal of Medical Virology 83(6), pp. 1023-1030. (10.1002/jmv.21889)
- Coles, S., Wang, E. C. Y., Man, S. T., Hills, R. K., Burnett, A. K., Tonks, A. and Darley, R. L. 2011. CD200 expression suppresses natural killer cell function and directly inhibits patient anti-tumor response in acute myeloid leukemia. Leukemia 25(5), pp. 792-799. (10.1038/leu.2011.1)
- Campo, M. S. et al. 2010. HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells. Virology 407(1), pp. 137-142. (10.1016/j.virol.2010.07.044)
- Coles, S., Man, S. T., Hills, R. K., Wang, E. C. Y., Burnett, A. K., Darley, R. L. and Tonks, A. 2010. Over-expression of CD200 un acute myeloid leukemia mediates the expansion of regulatory T-lymphocytes and directly inhibits natural killer cell tumor immunity [Abstract]. Blood 116(21), pp. 218-218.
- Chan, P. K. S. et al. 2010. T-Cell response to human papillomavirus type 58 L1, E6, and E7 peptides in women with cleared infection, cervical intraepithelial neoplasia, or invasive cancer. Clinical and Vaccine Immunology 17(9), pp. 1315-1321. (10.1128/CVI.00105-10)
- Thomas, K. J., Smith, K. L., Youde, S. J., Evans, M., Fiander, A. N., Borysiewicz, L. K. and Man, S. T. 2008. HPV16 E629-38-specific T cells kill cervical carcinoma cells despite partial evasion of T-cell effector function. International Journal of Cancer 122(12), pp. 2791-2799. (10.1002/ijc.23475)
- Capper, R. et al. 2007. The nature of telomere fusion and a definition of the critical telomere length in human cells. Genes and Development 21(19), pp. 2495-2508. (10.1101/gad.439107)
- McCarthy, C., Youde, S. J. and Man, S. T. 2006. Definition of an HPV18/45 cross-reactive human T-cell epitope after DNA immunisation of HLA-A2/KB transgenic mice. International Journal of Cancer 118(10), pp. 2514-21. (10.1002/ijc.21643)
- Fiander, A. N. et al. 2006. Prime-boost vaccination strategy in women with high-grade, noncervical anogenital intraepithelial neoplasia: clinical results from a multicenter phase II trial. International Journal of Gynecological Cancer 16(3), pp. 1075-1081. (10.1111/j.1525-1438.2006.00598.x)
- Youde, S. J., McCarthy, C. M., Thomas, K. J., Smith, K. L. and Man, S. T. 2005. Cross-typic specificity and immunotherapeutic potential of a human HPV16 E7-specific CTL line. International Journal of Cancer 114(4), pp. 606-12. (10.1002/ijc.20779)
- Smith, K. L., Tristram, A. J., Gallagher, K. M., Fiander, A. N. and Man, S. T. 2005. Epitope specificity and longevity of a vaccine-induced human T cell response against HPV18. International Immunology 17(2), pp. 167-176. (10.1093/intimm/dxh197)
- Hill, S. C. et al. 2005. Activation of CD40 in cervical carcinoma cells facilitates CTL responses and augments chemotherapy-induced apoptosis. Journal of Immunology 174(1), pp. 41-50.
- Wall, S. R. et al. 2005. Cervical human papillomavirus infection and squamous intraepithelial lesions in rural Gambia, West Africa: viral sequence analysis and epidemiology. British Journal of Cancer 93(9), pp. 1068-1076. (10.1038/sj.bjc.6602736)
- Lyons, G. E., Roszkowski, J. J., Man, S. T., Yee, C., Kast, W. M. and Nishimura, M. I. 2005. T-cell receptor tetramer binding or the lack there of does not necessitate antigen reactivity in T-cell receptor transduced T cells. Cancer Immunology, Immunotherapy 55(9), pp. 1142-1150. (10.1007/s00262-005-0103-9)
- Man, S. T., McMichael, A. J., Stauss, H. J. and Savage, P. 2004. Use of B cell-bound HLA-A2 class I monomers to generate high-avidity, allo-restricted CTLs against the leukemia-associated protein Wilms tumor antigen. Blood 103(12), pp. 4613-4615. (10.1182/blood-2003-11-3903)
- Smyth, L. J. C. et al. 2004. Immunological responses in women with human papillomavirus type 16 (HPV-16)-associated anogenital intraepithelial neoplasia induced by heterologous prime-boost HPV-16 oncogene vaccination. Clinical Cancer Research 10(9), pp. 2954-2961. (10.1158/1078-0432.CCR-03-0703)
- Adams, M. et al. 2003. Dendritic cell (DC) based therapy for cervical cancer: use of DC pulsed with tumour lysate and matured with a novel synthetic clinically non-toxic double stranded RNA analogue poly [I]:poly [C(12)U] (Ampligen R). Vaccine 21(7-8), pp. 787-90. (10.1016/S0264-410X(02)00599-6)
- Palmowski, M. J. et al. 2002. Competition between CTL narrows the immune response induced by prime-boost vaccination protocols. The Journal of Immunology 168(9), pp. 4391-4398. (10.4049/jimmunol.168.9.4391)
- Savage, P. et al. 2002. Induction of viral and tumour specific CTL responses using antibody targeted HLA class I peptide complexes. British Journal of Cancer 86(8), pp. 1336-1342. (10.1038/sj.bjc.6600223)
- Savage, P. et al. 2002. Anti-viral cytotoxic T cells inhibit the growth of cancer cells with antibody targeted hla class I/peptide complexes in scid mice. International Journal of Cancer 98(4), pp. 561-566. (10.1002/ijc.10219)
- Evans, M. et al. 2001. Antigen processing defects in cervical carcinomas limit the presentation of a CTL epitope from human papillomavirus 16 E6. The Journal of Immunology 167(9), pp. 5420-5428.
- Man, S. T. and Fiander, A. N. 2001. Immunology of human papillomavirus infection in lower genital tract neoplasia [review]. Best Practice & Research Clinical Obstetrics & Gynaecology 15(5), pp. 701-714. (10.1053/beog.2001.0215)
- Adams, M. et al. 2001. Clinical studies of human papilloma vaccines in pre-invasive and invasive cancer. Vaccine 19(17-19), pp. 2549-2556. (10.1016/S0264-410X(00)00488-6)
- Lawson, T., Man, S. T., Williams, S., Boon, A. C. M., Zambon, M. and Borysiewicz, L. K. 2001. Influenza A antigen exposure selects dominant Vbeta17+ TCR in human CD8+ cytotoxic T cell responses. International Immunology 13(11), pp. 1373-1381. (10.1093/intimm/13.11.1373)
- Lawson, T. et al. 2001. Functional differences between influenza A-specific cytotoxic T lymphocyte clones expressing dominant and subdominant TCR. International Immunology 13(11), pp. 1383-1390. (10.1093/intimm/13.11.1383)
- Youde, S. J., Dunbar, P. R. R., Evans, E. M. L., Fiander, A. N., Borysiewicz, L. K., Cerundolo, V. and Man, S. T. 2000. Use of fluorogenic histocompatibility leukocyte antigen-A*0201/HPV 16 E7 peptide complexes to isolate rare human cytotoxic T-lymphocyte-recognizing endogenous human papillomavirus antigens. Cancer Research 60(2), pp. 365-371.
- Nimako, M., Fiander, A. N., Wilkinson, G. W. G., Borysiewicz, L. K. and Man, S. T. 1997. Human papillomavirus-specific cytotoxic T lymphocytes in patients with cervical intraepithelial neoplasia grade III. Cancer Research 57(21), pp. 4855-4861.
- Fiander, A. N., Man, S. T., Borysiewicz, L. K. and Wilkinson, G. W. G. 1997. Therapeutic vaccines for cervical cancer: concept and clinical results. Biodrugs -Auckland- 8(5), pp. 331-338. (10.2165/00063030-199708050-00001)
- Borysiewicz, L. K. et al. 1996. A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer. The Lancet 347(9014), pp. 1523-1527. (10.1016/s0140-6736(96)90674-1)
- Borysiewicz, L. K. et al. 1995. Development and initial clinical studies of TA-HPV in cervical cancer. European Journal of Cancer 31(supp 3), pp. 17-17. (10.1016/0959-8049(95)99882-z)
Book sections
- Tabi, Z. and Man, S. 2008. Cancer vaccines and immune monitoring (an overview). In: Hayat, M. A. ed. General methods and overviews, lung carcinoma and prostate carcinoma:. Methods of cancer diagnosis, therapy and prognosis Vol. 2. Springer, pp. 129-160., (10.1007/978-1-4020-8442-3)
- Fiander, A. N. and Man, S. T. 2003. Antiviral vaccination for treating intraepithelial neoplasia. In: Maclean, A. B., Singer, A. and Critchley, H. eds. Lower Genital Tract Neoplasia. London: RCOG Press, pp. 192-209.
- Adams, M. et al. 2001. Clinical studies of human papilloma vaccines in cervical cancer. In: Mackiewicz, A., Kurpisz, M. and Zeromski, J. eds. Progress in Basic and Clinical Immunology. Advances in Experimental Medicine and Biology Vol. 442. New York: Kluwer Academic/Plenum Publishers, pp. 419-427., (10.1007/978-1-4615-0685-0_61)
- Man, S. T. 2001. Recognition of human tumours: viral antigens as immunological targets for cytotoxic T cells. In: Robbins, R. A. and Rees, R. eds. Cancer Immunology. Immunology and Medicine Vol. 30. Springer, pp. 123-145.
- Evans, M., Man, S. T. and Borysiewicz, L. K. 2000. Vaccine strategies for cancer. In: Weissberg, P. ed. Horizons in Medicine., Vol. 12. London: Royal College of Physicians, pp. 289-300.
- Borysiewicz., L. K. and Man, S. T. 2000. Vaccinia-based human papillomavirus vaccines in cervical cancer. In: Stern, P. L., Beverley, P. C. L. and Carroll, M. W. eds. Cancer vaccines and immunotherapy. Cambridge, UK: Cambridge University Press, pp. 62-81.
- Man, S. T., Evans, E. M. L., Nimako, M. and Borysiewicz, L. K. 1999. Recombinant vaccinia virus. In: Tindle, R. W. ed. Vaccines for Human Papillomavirus Infection and anogenital disease, 14th ed.. Medical Intelligence Unit Austin, Texas: R.G. Landes Company, pp. 69-90.
Ymchwil
Mae fy ymchwil yn canolbwyntio ar rôl y system imiwnedd mewn canser, yn enwedig ceisio datblygu ffyrdd newydd o drin canser neu fonitro statws y system imiwnedd i adnabod cleifion prognosis gwael. Dros y 5 mlynedd diwethaf rwyf wedi bod yn gweithio mewn tîm sy'n ymroddedig i astudio lewcemia lymffocytig cronig (CLL). Mae gan fy labordy dri phrif bwnc ymchwil:
Targedau Penodol Tiwmor
Ar gyfer therapi canser effeithiol, rhaid targedu celloedd T yn benodol at gelloedd canser ond nid achosi niwed i feinwe iach arferol. Yn ddelfrydol, dylai targedau celloedd T fod yn berthnasol i ystod eang o ganserau dynol.
Dangosom brawf o gysyniad ar gyfer math newydd o antigen tiwmor, yn seiliedig ar briodweddau biolegol cynhenid celloedd canser. Dangoswyd bod clon celloedd CD8+ T, sy'n cydnabod epitopau peptid sy'n deillio o brotein Bax hollbresennol, yn adnabod ystod eang o gelloedd tiwmor gan gynnwys celloedd CLL cynradd. Rydym wedi datblygu technegau i ynysu celloedd T gan gydnabod yr epitop hwn gan roddwyr iach a chleifion CLL. Gellir tyfu'r celloedd T hyn i niferoedd mawr ac mae astudiaethau pellach sy'n archwilio eu potensial therapiwtig ar gyfer CLL ar y gweill.
Atal imiwnedd neu oddefgarwch
Mae cynhyrchu ymatebion imiwnedd effeithiol mewn cleifion canser yn cael ei rwystro gan ataliad celloedd T neu oddefgarwch a achosir gan gelloedd canser.
Mewn cydweithrediad â chydweithwyr o Haematoleg, rydym wedi astudio mecanweithiau atal imiwnedd gan ddefnyddio lewcemia myeloid acíwt (AML; Darley a Tonks) a lewcemia lymffocytig cronig (CLL; Pepper and Fegan). Nododd yr astudiaethau hyn rôl bwysig ar gyfer CD200 wrth atal imiwnedd cellog yn AML®. Ar gyfer CLL, gwelsom fod cleifion yn dangos ehangu yn aml yn eu his-set celloedd CD8+ T. Achosodd hyn wrthdroad yn y gymhareb CD4:CD8, ac roedd gan gleifion o'r fath prognosis clinigol tlotach. Cyfoethogwyd y celloedd CD8 + T mewn cleifion CLL ar gyfer celloedd T gwahaniaethol terfynol, ac ar gyfer mynegiant PD-1, gan awgrymu camweithrediad imiwnedd. Ar hyn o bryd rydym yn ymchwilio i swyddogaeth a phenodoldeb yr is-set celloedd T estynedig hon, a'r defnydd posibl o "lofnodion celloedd T" i nodi cleifion a fydd yn datblygu clefyd ymosodol.
Peptidau anarferol a gydnabyddir gan CD8+ T-gelloedd
Yn ddiweddar, gwnaethom y canfyddiad rhyfeddol y gallai clôn celloedd CD8+ T dynol gydnabod peptid synthetig a oedd wedi'i addasu trwy ychwanegu cadwyn ochr t Bu (LLSY(3-tBu)FGTPT). Nid yw addasiadau tBu o'r fath yn digwydd o ran natur ac nid yw eu heffaith biolegol yn hysbys. Ar ben hynny, methodd clôn celloedd T ag ymateb yn erbyn y peptid math gwyllt cyfatebol nas addaswyd (LLSYFGTPT). Nid oedd gwahaniaeth amlwg rhwng y peptidau o ran rhwymo i foleciwlau HLA-A2. Felly mae'n ymddangos y gall y clôn celloedd T hwn wahaniaethu rhwng dau peptid sy'n wahanol yn unig gan addasiad un gadwyn ochr. Yn ddiweddar rydym wedi cael cyllid gan Ymddiriedolaeth Wellcome ar gyfer prosiect trawsddisgyblaethol a fydd yn cynnwys cydweithio rhwng imiwnolegwyr, cemegwyr peptid a biolegwyr strwythurol. Bydd y prosiect hwn yn trafod y cwestiynau canlynol:
- Beth yw'r ligand peptid "naturiol" a gydnabyddir gan y clon celloedd T?
- Beth yw'r sail strwythurol ar gyfer adnabod y peptid synthetig?
- A all addasiadau cadwyn ochr synthetig fodiwleiddio swyddogaeth celloedd CD8 + T?
Bydd rhan o'r prosiect yn cynnwys datrys strwythurau crisial o gyfadeiladau peptid 3 HLA-A2: o leiaf, ac archwilio effaith swyddogaethol addasiadau ar swyddogaeth celloedd CD8 + T. Gallai'r wybodaeth a gafwyd o'r prosiect hwn arwain at ddylunio asiantau synthetig i hybu neu atal ymatebion imiwnedd.
Cyllid Ymchwil (5 mlynedd diwethaf)
- 2020 Grant Prosiect Prostate Cancer UK "Ailosodwch y microamgylchedd imiwnedd tiwmor" £227,727 (Cyd-I gyda'r Athro Clayton a Errington)
- Ymchwil Canser Cymru 2017. Efrydiaeth "Mae rôl celloedd CD4+ T yn is-setiau o ran dilyniant clefydau ac ymateb i driniaeth yn CLL" £90,764 (PI)
- Gwobr Trawsddisgyblaethol Wellcome ISSF 2015 "Effaith strwythurol a swyddogaethol addasu peptidau cadwyn ochr a gydnabyddir gan CD8+ T-gelloedd" £40,000 (PI)
- 2015 Tenovus PhD Efrydiaeth " A yw bôn-gelloedd y prostad yn agored i ladd celloedd T? £89,781 (Cyd-I gyda Dr Z.Tabi (PI)).
Addysgu
Fi yw'r arweinydd addysgu ar gyfer yr Is-adran Canser a Geneteg, gan gysylltu â C4ME a darparu cefnogaeth ar gyfer gweithgareddau addysgu sy'n gysylltiedig ag addysgu myfyrwyr meddygol UG.
Rwy'n darlithio ac yn perfformio asesiadau cwrs ar gyfer y Modiwlau Imiwnoleg Uwch (ME3045) ac Imiwnopatholeg ac Imiwnotherapi (ME3046).
Ar hyn o bryd, rwy'n diwtor personol i 12 o fyfyrwyr.
Rwy'n goruchwylio prosiectau SSC ar gyfer myfyrwyr meddygol, sy'n cynnwys prosiectau llenyddiaeth ar gyfer blwyddyn 1, prosiectau labordy ar gyfer blwyddyn 2 a phrosiectau wedi'u harwain gan diwtoriaid/prosiectau pwrpasol ar gyfer blynyddoedd 3 a 4. Ers 2016 rwyf wedi goruchwylio 27 o fyfyrwyr meddygol ar brosiectau ymgysylltu â'r gymuned (Gweithdai Iechyd Rhyngweithiol ar gyfer Ysgolion Cynradd Cymru). Mae mwy o fanylion ar gael o dan y tab Ymgysylltu.
Rwy'n cyfweld myfyrwyr ysgol feddygol (MMIs).
Bywgraffiad
Trosolwg Gyrfa
- 2012-presennol: Darllenydd, Is-adran Canser a Geneteg, Ysgol Meddygaeth, Prifysgol Caerdydd
- 2002-2012: Uwch Ddarlithydd, Haint ac Imiwnedd, Ysgol Meddygaeth, Prifysgol Caerdydd
- 1995-2003: Cymrawd Ymchwil Prifysgol y Gymdeithas Frenhinol, Adran Meddygaeth, Coleg Meddygaeth Prifysgol Cymru
- 1994-1995: Cymrawd Ymchwil Ôl-ddoethurol, Adran Meddygaeth, Coleg Meddygaeth Prifysgol Cymru
- 1990-1994: Cymrawd Ymchwil Ôl-ddoethurol, Adran Microbioleg, Prifysgol Virginia, UDA
Aelodaethau proffesiynol
- Aelod o Gymdeithas Imiwnoleg Prydain
Meysydd goruchwyliaeth
I am interested in supervising PhD students in the following areas:
- Cancer Immunology, in particular Leukaemia
- Immunotherapy
- Novel tumour antigens
- Therapeutic cancer vaccines
- Overcoming cancer associated immunosuppression
- T cells as biomarkers for disease progression and/or response to treatment
Ymgysylltu
Rwyf wedi bod yn weithgar mewn sawl agwedd ar ymgysylltu â'r cyhoedd:
- Gweithdai Iechyd Rhyngweithiol. Mae'r rhain wedi cael eu rhedeg gan fyfyrwyr meddygol fel rhan o'u prosiectau SSC 3ydd neu 4edd flwyddyn. Mae'r myfyrwyr yn ymweld ag ysgolion cynradd Cymru i ddysgu plant (9-11 oed) am y corff dynol a byw'n iach. Mae'r gweithdai yn cynnwys gweithgareddau, arddangosiadau a chwisiau "ymarferol" sydd wedi'u cynllunio i gadw sylw'r plant ac ot yn gwneud dysgu'n hwyl. Dechreuwyd y prosiect ar ei ffurf bresennol drwy gyllid gan brosiect Cyfnewid CIty Rhanbarth Prifysgol Caerdydd. Hyd yn hyn, ymwelwyd â 49 o ysgolion yng Nghaerdydd, Caerffili, Methyr Tudfull a Phontypridd.
- Gwyddoniaeth mewn Iechyd. Rwyf wedi cynnal myfyrwyr profiad gwaith (Blwyddyn 12) yn fy labordy.
- Cynyddu dealltwriaeth y cyhoedd o wyddoniaeth, yn enwedig imiwnoleg canser. Rwyf wedi rhoi sgyrsiau i godwyr arian elusen a grwpiau cymorth i gleifion.