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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Targeting the tumor microenvironment in genitourinary cancers: current progress and future directions in prostate
1Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Introduction:
Prostate cancer is no longer considered a 'cold' tumor; several novel immune platforms are now capable of overcoming obstructive cellular and soluble impediments within the tumor microenvironment (TME) thus fostering the entry of immune effector cells. Antitumor responses are supported by favorable changes in conventional and molecular imaging and the serum biomarker, prostate-specific antigen (PSA).
Areas Covered:
This review briefly outlines the current promising strategies with multispecific antibodies such as T-cell engagers, and adoptive cellular therapeutics with chimeric antigen receptor T cells that have successfully gained entry into the tumor microenvironment and generated innate and adaptive immune responses in this disease. These results provide ongoing impetus to pursue immunotherapies in solid tumors, especially those not thought to be enriched with immune cells.
Expert Opinion:
Ongoing research is providing strong evidence that a 'cold' tumor, such as metastatic castration-resistant prostate cancer (mCRPC), can now respond to unique immunologic constructs. It may be possible to bring these treatments earlier in the disease continuum, even as neoadjuvant therapies.
Insights
Prostate cancer is now treatable with novel immunotherapies that overcome tumor microenvironment barriers. These approaches, including T cell engagers and CAR T cells, are effective in metastatic castration-resistant prostate cancer.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Prostate cancer, once considered immunologically 'cold,' is now a target for immunotherapy.
- The tumor microenvironment (TME) presents significant barriers to immune effector cell infiltration.
- Novel immune platforms are emerging to overcome these TME impediments.
Purpose of the Study:
- To review current promising immunotherapeutic strategies for prostate cancer.
- To highlight advancements in overcoming the TME in prostate cancer.
- To discuss the potential of immunotherapies in solid tumors, including prostate cancer.
Main Methods:
- Review of multi-specific antibodies, including T cell engagers.
- Examination of adoptive cellular therapeutics, such as chimeric antigen receptor T cells.
- Analysis of immune responses within the tumor microenvironment.
Main Results:
- Novel immune platforms successfully infiltrate the TME in prostate cancer.
- Favorable changes in imaging and prostate-specific antigen (PSA) levels indicate anti-tumor responses.
- Immunotherapies demonstrate efficacy in metastatic castration-resistant prostate cancer (mCRPC).
Conclusions:
- Prostate cancer is responsive to novel immunologic constructs, challenging its 'cold' tumor status.
- Immunotherapies are gaining traction for solid tumors, even those with low immune cell infiltration.
- Early application of these immunotherapies, potentially as neoadjuvant treatments, is a promising future direction.
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