Peptide vaccination against multiple myeloma using peptides derived from anti-apoptotic proteins: a phase I trial

Jørgensen, Nicolai Grønne Dahlager; Ahmad, Shamaila Munir; Abildgaard, Niels; Straten, Per thor; Svane, Inge Marie; Andersen, Mads Hald; Knudsen, Lisbeth B.

doi:10.21037/sci.2016.11.09

Cited by 15 publications

(11 citation statements)

References 16 publications

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“…These preclinical studies supported the passage to Phase I trial evaluation of therapeutic vaccination with peptides from Bcl-2, Bcl-xL and Mcl-1 in patients with relapse MM (NCT01272466). In this study, vaccines were given in combination to treatment with bortezomib [183]. This vaccination was well tolerated and the signs of toxicity were all attributed to bortezomib.…”

Section: Vaccination Using Anti-apoptotic Protein-derived Peptidesmentioning

confidence: 99%

Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer

D’Aguanno

Bufalo

2020

Cells

108

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The dynamic interplay between pro-death and pro-survival Bcl-2 family proteins is responsible for a cell’s fate. Due to the recognized relevance of this family in cancer progression and response to therapy, different efforts have made in recent years in order to develop small molecules able to target anti-apoptotic proteins such as Bcl-2, Bcl-xL and Mcl-1. The limitations of the first Bcl-2 family targeted drugs, regarding on-target and off-target toxicities, have been overcome with the development of venetoclax (ABT-199), the first BH3 mimetic inhibitor approved by the FDA. The purpose of this review is to discuss the state-of-the-art in the development of drugs targeting Bcl-2 anti-apoptotic proteins and to highlight the potential of their application as single agents or in combination for improving anti-cancer therapy, focusing in particular on solid tumors.

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Section: Vaccination Using Anti-apoptotic Protein-derived Peptidesmentioning

confidence: 99%

Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer

D’Aguanno

Bufalo

2020

Cells

108

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“…Cancer vaccines have been shown to generate potent immune responses that can translate into clinically meaningful improvements in outcomes for patients 184. In multiple myeloma, many such approaches have been tested including an idiotype DNA vaccine,185 peptide derived from Bcl-2 family vaccine,186 gene transduced tumor cell vaccine (GVAX),187188 idiotype loaded antigen presenting cells,189 and whole cell dendritic cell/myeloma fusion vaccine 184190191. Most recently, multipeptide vaccine PVX-410 with or without lenalidomide was tested in 22 patients with smoldering multiple myeloma, and results suggested that the vaccine was safe and immunogenic 192.…”

Section: Future Directionsmentioning

confidence: 99%

Emerging immunotherapies in multiple myeloma

Shah

Mailankody

2020

BMJ

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Despite considerable advances in treatment approaches in the past two decades, multiple myeloma remains an incurable disease. Treatments for myeloma continue to evolve with many emerging immunotherapies. The first immunotherapy used to treat hematologic cancers, including multiple myeloma, was an allogeneic stem cell transplant. In the mid-2000s, immunomodulatory drugs thalidomide, lenalidomide, and subsequently pomalidomide were proven to be effective in multiple myeloma and substantially improved survival. The next wave of immunotherapies for multiple myeloma included the monoclonal antibodies daratumumab and elotuzumab, which were approved by the Food and Drug Administration in 2015. Subsequently, a variety of immunotherapies have been developed for multiple myeloma, including chimeric antigen receptor T cells, bispecific antibodies, antibody drug conjugates, and checkpoint inhibitors. Many of these emerging treatments target the B cell maturation antigen, which is expressed on plasma cells, although several other novel receptors are also being studied. This review summarizes the evidence of these various immunotherapies, their mechanism of action, and data from clinical trials regarding the treatments’ safety and efficacy.

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“…Additionally, phase 1 clinical trials examining the effects of BCL-2-family-targeted vaccines and PD-L1-targeted vaccines have demonstrated an acceptable safety profile as well as the ability to induce an immune response [ 174 , 175 ].…”

Section: Vaccinesmentioning

confidence: 99%

Keeping Myeloma in Check: The Past, Present and Future of Immunotherapy in Multiple Myeloma

Ackley

Ochoa

Ghoshal

et al. 2021

Cancers

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Multiple myeloma is an incurable disease of malignant plasma cells and an ideal target for modern immune therapy. The unique plasma cell biology maintained in multiple myeloma, coupled with its hematological nature and unique bone marrow microenvironment, provide an opportunity to design specifically targeted immunotherapies that selectively kill transformed cells with limited on-target off-tumor effects. Broadly defined, immune therapy is the utilization of the immune system and immune agents to treat a disease. In the context of multiple myeloma, immune therapy can be subdivided into four main categories: immune modulatory imide drugs, targeted antibodies, adoptive cell transfer therapies, and vaccines. In recent years, advances in all four of these categories have led to improved therapies with enhanced antitumor activity and specificity. In IMiDs, modified chemical structures have been developed that improve drug potency while reducing dose limiting side effects. Targeted antibody therapies have resulted from the development of new selectively expressed targets as well as the development of antibody drug conjugates and bispecific antibodies. Adoptive cell therapies, particularly CAR-T therapies, have been enhanced through improvements in the manufacturing process, as well as through the development of CAR constructs that enhance CAR-T activation and provide protection from a suppressive immune microenvironment. This review will first cover in-class breakthrough therapies for each of these categories, as well as therapies currently utilized in the clinic. Additionally, this review will explore up and coming therapeutics in the preclinical and clinical trial stage.

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Peptide vaccination against multiple myeloma using peptides derived from anti-apoptotic proteins: a phase I trial

Cited by 15 publications

References 16 publications

Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer

Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer

Emerging immunotherapies in multiple myeloma

Keeping Myeloma in Check: The Past, Present and Future of Immunotherapy in Multiple Myeloma

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