To date, clinical trials of immunotherapy in patients with solid tumors have been somewhat disappointing, with response rates less than would be predicted by standard transplantable models. It seems increasingly unlikely that immunotherapy alone will prove sufficient to control advanced cancer. Thus, the development of combination strategies involving radiation, chemotherapy, and androgen manipulation as well as immune checkpoint blockade is critical to achieve clinical success. Testing a variety of combination approaches is impractical in the clinic but is achievable using a targeted model approach involving transgenic animals that spontaneously develop prostate cancer. The full genetic characterization of the specific T cells rendered unresponsive by cancer forms the scientific basis for this approach, and has the potential to define new molecular targets and pathways to augment vaccine efficacy. Finally, characterization of patients'' immune response to prostate cancer in the presence or absence of vaccination will determine new cellular targets for vaccination. In summary, the Drake laboratory has undertaken an interactive approach in which discoveries in the laboratory guide clinical trial development, and the results of these trials will feed back to the laboratory to further refine and expand the role of immunotherapy approaches for patients with prostate cancer.
SKCCC Flow Cytometry
Phase 3 Clinical Trial for Advanced Stage Prostate Cancer
Zeng J, Harris TJ, Lim M, Drake CG, Tran PT. "Immune Modulation and Stereotactic Radiation: Improving Local and Abscopal Responses." Biomed Res Int. 2013;2013:658126. Epub 2013 Nov 14.
Drake CG, Sharma P, Gerritsen W. "Metastatic castration-resistant prostate cancer: new therapies, novel combination strategies and implications for immunotherapy." Oncogene. 2013 Nov 25. doi: 10.1038/onc.2013.497. [Epub ahead of print].
Drake CG, Lipson EJ, Brahmer JR. "Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer." Nat Rev Clin Oncol. 2014 Jan;11(1):24-37. doi: 10.1038/nrclinonc.2013.208. Epub 2013 Nov 19.
Wada S, Harris TJ, Tryggestad E, Yoshimura K, Zeng J, Yen HR, Getnet D, Grosso JF, Bruno TC, De Marzo AM, Netto GJ, Pardoll DM, DeWeese TL, Wong J, Drake CG. "Combined treatment effects of radiation and immunotherapy: studies in an autochthonous prostate cancer model." Int J Radiat Oncol Biol Phys. 2013 Nov 15;87(4):769-76. doi: 10.1016/j.ijrobp.2013.07.015. Epub 2013 Sep 21
Nirschl CJ, Drake CG. ‘Molecular pathways: coexpression of immune checkpoint molecules: signaling pathways and implications for cancer immunotherapy." Clin Cancer Res. 2013 Sep 15;19(18):4917-24. doi: 10.1158/1078-0432.CCR-12-1972. Epub 2013 Jul 18.
Compositions and Methods for Modulating an Immune Response
Patent # WO 2009137095 A2 | 11/12/2009
Compositions and methods for modulating an immune response.