Peptide vaccination against multiple myeloma using peptides derived from anti-apoptotic proteins: a phase I trial
Nicolai Grønne Jørgensen1, Shamaila Munir Ahmad1, Niels Abildgaard2
1Center for Cancer Immunotherapy (CCIT), Department of Hematology, Herlev and Gentofte Hospital, Herlev, Denmark.
Abstract:
The B-cell lymphoma-2 (Bcl-2) family of proteins play a crucial role in multiple myeloma (MM), contributing to lacking apoptosis which is a hallmark of the disease. This makes the Bcl-2 proteins interesting targets for therapeutic peptide vaccination. We report a phase I trial of therapeutic vaccination with peptides from the proteins Bcl-2, Bcl-XL and Mcl-1 in patients with relapsed MM. Vaccines were given concomitant with bortezomib. Out of 7 enrolled patients, 4 received the full course of 8 vaccinations. The remaining 3 patients received fewer vaccinations due to progression, clinical decision of lacking effect and development of hypercalcemia, respectively. There were no signs of toxicity other than what was to be expected from bortezomib. Immune responses to the peptides were seen in all 6 patients receiving more than 2 vaccinations. Three patients had increased immune responses after vaccination. Vaccination against Bcl-2 was well tolerated and was able to induce immune responses in patients with relapsed MM.
Insights
Therapeutic peptide vaccination targeting B-cell lymphoma-2 (Bcl-2) proteins in relapsed multiple myeloma (MM) was well-tolerated. This approach successfully induced immune responses in patients, offering a potential new strategy for MM treatment.
Area of Science:
- Oncology
- Immunology
- Clinical Trials
Background:
- The B-cell lymphoma-2 (Bcl-2) protein family is implicated in multiple myeloma (MM) pathogenesis by inhibiting apoptosis.
- Targeting Bcl-2 proteins presents a potential therapeutic strategy for MM due to their role in disease survival.
- Therapeutic peptide vaccination offers a novel approach to elicit anti-cancer immune responses.
Purpose of the Study:
- To evaluate the safety and immunogenicity of a therapeutic peptide vaccination targeting Bcl-2 family proteins in patients with relapsed multiple myeloma.
- To assess the immune response induced by vaccination with peptides from Bcl-2, Bcl-XL, and Mcl-1 proteins.
- To investigate the feasibility of combining Bcl-2 peptide vaccination with bortezomib therapy.
Main Methods:
- Phase I clinical trial design.
- Enrollment of 7 patients with relapsed multiple myeloma.
- Administration of peptide vaccines targeting Bcl-2, Bcl-XL, and Mcl-1, concurrently with bortezomib.
- Monitoring for toxicity and assessment of immune responses to the vaccine peptides.
Main Results:
- The vaccination regimen was well-tolerated, with no unexpected toxicities beyond those associated with bortezomib.
- Immune responses to the vaccine peptides were observed in 6 out of 7 patients who received more than two vaccinations.
- Three patients demonstrated enhanced immune responses following the vaccination course.
- Vaccination was successfully administered in conjunction with bortezomib therapy.
Conclusions:
- Therapeutic peptide vaccination targeting Bcl-2 proteins is a safe and feasible approach in patients with relapsed multiple myeloma.
- The vaccination strategy can effectively induce immune responses in the target patient population.
- This study supports further investigation of Bcl-2-targeted peptide vaccination as a potential therapeutic modality for multiple myeloma.
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