19 Dec Neoantigens Can Stimulate Immunity in Relapsed Multiple Myeloma
MedicalResearch.com Interview with:
Dr. Samir Parekh, MBBS
Medicine, Hematology and Medical Oncology
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study? Would you briefly describe what is meant by ‘neoantigens’? How might they be used to stimulate immunity in a multiple myeloma patients?
Response: Myeloma is considered a “cold” tumor for immunotherapy (as compared to some solid tumors such as melanoma) given the relatively fewer DNA mutations in an average myeloma patient. Our clinical experience suggests that this may not be totally correct. Our findings focus on mutations that can become antigens (neo-antigens) and challenges the stereotype. We can create vaccines based on peptides resulting from these mutations to stimulate immune responses.
MedicalResearch.com: What are the main findings?
- We demonstrate an increase in neoantigen load in relapsed multiple myeloma patients as compared to newly diagnosed MM patients.
- Moreover, we identify shared neoantigens across multiple patients in three multiple myeloma oncogenic driver genes (KRAS, NRAS and IRF4).
- Next, we validate neoantigen T cell response and clonal expansion in correlation with clinical response in relapsed multiple myeloma patients.
This is the first study to experimentally validate the immunogenicity of predicted neoantigens from next generation sequencing in relapsed multiple myeloma patients.
MedicalResearch.com: What should readers take away from your report?
Response: T cell responses could serve as a direct pharmacodynamics biomarker of immunotherapeutic interventions in myeloma and neoantigens could be targeted by neoantigen targeting cancer vaccines in the future.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Our results provide the foundation for using neoantigen targeting strategies such as peptide vaccines in future trials for multiple myeloma patients.
MedicalResearch.com: Is there anything else you would like to add? Any disclosures?
Prof. Nina Bhadrwaj (co-author) and colleagues are pursuing a clinical trial (PGV-001, NCT02721043) investigating the safety and immunogenicity of a personalized, multipeptide, neoantigen vaccine for the treatment.
Mutation-derived Neoantigen-specific T-cell Responses in Multiple Myeloma
Deepak Perumal, Naoko Imai, Alessandro Laganà, John Finnigan, David Melnekoff, Violetta V. Leshchenko, Alexander Solovyov, Deepu Madduri, Ajai Chari, Hearn Jay Cho, Joel T. Dudley, Joshua D. Brody, Sundar Jagannath, Benjamin Greenbaum, Sacha Gnjatic, Nina Bhardwaj and Samir Parekh
Clin Cancer Res December 19 2019 DOI:10.1158/1078-0432.CCR-19-2309
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