Current Funding: DoD CDMRP PCRP, PC210330, 09/31/22 - 08/31/25. Grant Total: $1,182,038. Dr. Labros Meimetis (PI).

Previous Funding: Catacosinos Cancer Translational Researcher Award, Stony Brook Foundation, 11/1/21 - 05/31/22. Grant Total: $30,000. Dr. Labros Meimetis (PI).

Publications: Śmiłowicz, D.; Schlyer, D.; Boros, E.; Meimetis, L. "Evaluation of a RadioIMmunostimulant (RIMS) in a syngeneic model of murine prostate cancer and immunoPET analysis of T-Cell distribution." Molecular Pharmaceutics. 2022, 19 (9), 3217-3227. https://doi.org/10.1021/acs.molpharmaceut.2c00361

Rationale: Metastatic castrate resistant prostate cancer (mCRPC) is incurable and the most lethal form of prostate cancer. Of the estimated 3 million prostate cancer patients in the US (2022), ~50K deaths are attributed to mCRPC annually. The 5-yr survival rate for patients with mCRPC is ~15%. Two main features contribute to the resilience of mCRPC to treatment: 1) A highly immunosuppressive tumor microenvironment, meaning that the body’s immune system is ineffective in suppressing tumor growth. Immunotherapies that show significant patient benefit in other cancer types, have no effect towards mCRPC. Currently, no approved therapy can effectively convert an immunosuppressive tumor microenvironment into an immune responsive state in mCRPC. 2) The second major challenge in treating mCRPC is tumor heterogeneity. The majority of mCRPC patients possess subpopulations of cancer cells with distinct morphological and genetic profiles that exhibiting different behaviors and response rates to therapies. Tumor heterogeneity explains why chemotherapies against mCRPC have limited benefit. Most cancer drugs are designed to kill cells by disrupting specific receptors, enzymes or cellular division. Therefore, even small subpopulations of cells in a tumor that are not susceptible to a drugs mechanism of action, will evade cell death and continue growing after treatment.

In summary, a highly immunosuppressive tumor microenvironment and substantial tumor heterogeneity, makes treatment of mCRPC a significant clinical challenge.

Thus, the development of new drug paradigms that induces an immune response to prevent tumor growth and effectively kills all subpopulations of cancer cells in heterogeneous tumors, would be highly significant and have a tremendous impact in treating mCRPC.

Objective: We have developed a new drug paradigm, RadioIMmunoStimulant (RIMS), to addresses the clinical challenges in treating mCRPC, namely an immunosuppressive tumor microenvironment and tumor heterogeneity. RIMS accomplishes this by utilizing a therapeutic radiometal (M) that can kill a variety of cancer cell types and combines it with an immunostimulant payload that generates a long term adaptive immune response. Mechanistically, the cancer cell killing generated by the radiometal and the immune cell recruitment to the tumor elicited by the immunostimulant will synergize to generate a tumor vaccine in the body against heterogeneous tumors in mCRPC.