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Review
. 2023 Oct 17;4(10):101199.
doi: 10.1016/j.xcrm.2023.101199. Epub 2023 Sep 21.

Prostate cancer immunotherapy: Improving clinical outcomes with a multi-pronged approach

Dhivya Sridaran  1 , Elliot Bradshaw  1 , Carl DeSelm  2 , Russell Pachynski  3 , Kiran Mahajan  4 , Nupam P Mahajan  5
Affiliations
Review

Prostate cancer immunotherapy: Improving clinical outcomes with a multi-pronged approach

Dhivya Sridaran et al. Cell Rep Med. .

Abstract

Cancer immunotherapy has gained traction in recent years owing to remarkable tumor clearance in some patients. Despite the notable success of immune checkpoint blockade (ICB) in multiple malignancies, engagement of the immune system for targeted prostate cancer (PCa) therapy is still in its infancy. Multiple factors contribute to limited response, including the heterogeneity of PCa, the cold tumor microenvironment, and a low number of neoantigens. Significant effort is being invested in improving immune-based PCa therapies. This review is a summary of the status of immunotherapy in treating PCa, with a discussion of multiple immune modalities, including vaccines, adoptively transferred T cells, and bispecific T cell engagers, some of which are undergoing clinical trials. In addition, this review also focuses on emerging mechanism-based small-molecule tyrosine kinase inhibitors with immune modulatory properties that, either as single agents or in combination with other immunotherapies, have the potential to improve clinical outcomes.

Keywords: (R)-9b; AR; BiTE; CAR T cell therapy; CEP-11981; CRPC; CTC; ICB; SGI-9481; TKI; androgen receptor; cabozantinib; castration-resistant prostate cancer; ibrutinib; immune checkpoint blockade; pexidartinib; prostate cancer; small-molecule inhibitors; vaccine.

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Conflict of interest statement

Declaration of interests N.P.M. and K.M. are named as inventors of three patents (9,850,216, 10,017,478, and 10,336,734) related to the ACK1 inhibitor (R)-9b. The patents have been licensed by TechnoGenesys, Inc. N.P.M. and K.M are co-founders of TechnoGenesys, Inc., and own stocks and serve as consultants for TechnoGenesys, Inc.

Figures

None
Graphical abstract
Figure 1
Figure 1
Current and emerging immunotherapeutic options to treat prostate cancer Shown are the existing and emerging strategies for PCa immunotherapy. The classic immune checkpoint blockade (ICB) therapy uses monoclonal antibodies against PD-1/PD-L1/CTLA-4. ICB in combination with other therapies is currently being tested to maximize efficacy. Several DNA/RNA peptide vaccines have shown promise in inhibiting PCa growth. Generation and testing of novel fusion proteins and nucleic acid formulations are underway. T cell engagers and bispecific antibodies (BiTEs) that create cancer-destroying contact between immune cells and cancer cells is another proficient immunotherapy strategy gaining prominence. Profiling of circulating T cells (CTCs) to screen treatment-induced antigenic alterations and novel marker detection is emerging as an effective strategy for personalized therapeutic intervention ensuring generation of targeted antibodies with improved clinical efficiency. Multiple immune cell types bearing chimeric antigen receptors (CARs) are being engineered and tested for therapeutic efficacy against PCa. Targeting tyrosine kinases of molecular significance contributing to immunosuppression using small-molecule inhibitors and their combination with other immunotherapies also hold promise in improving existing PCa treatment regimens. Image was generated using BioRender.com.
See this image and copyright information in PMC

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