Advances in immunotherapy in multiple myeloma

Boussi, Leora; Niesvizky, Rubén

doi:10.1097/cco.0000000000000407

Cited by 14 publications

(12 citation statements)

References 67 publications

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“…Anticancer vaccination aims to re-educate host immunity, stimulate/expand tumor-specific effector cells, and generate long-term memory (25,26). Vaccine efficacy and response time depend on effector cell function/proliferation and tumor burden (26).…”

Section: Vaccinesmentioning

confidence: 99%

“…Recent anti-multiple myeloma vaccination approaches can be categorized into targeted antigen-and whole cell-based methodologies. Targeted antigen approaches include protein/peptide-based vac-cines that introduce tumor-associated antigens (TAA) to recruit native DCs for antigen processing/presentation and subsequent multiple myeloma-specific effector cell expansion (25). In the peritransplantation setting, studies have explored vaccines targeting MAGE-A3, hTERT, or survivin in conjunction with vaccine-primed autologous lymphocyte infusion (27)(28)(29).…”

Section: Vaccinesmentioning

confidence: 99%

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How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma

Cohen

Raje

Fowler

et al. 2020

Clinical Cancer Research

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The progression of multiple myeloma, a hematologic malignancy characterized by unregulated plasma cell growth, is associated with increasing innate and adaptive immune system dysfunction, notably in the T-cell repertoire. Although treatment advances in multiple myeloma have led to deeper and more durable clinical responses, the disease remains incurable for most patients. Therapeutic strategies aimed at overcoming the immunosuppressive tumor microenvironment and activating the host immune system have recently shown promise in multiple myeloma, particularly in the relapsed and/or refractory disease setting. As the efficacy of T-cell-dependent immuno-oncology therapy is likely affected by the health of the endogenous T-cell repertoire, these therapies may also provide benefit in alternate treatment settings (e.g., precursor disease; after stem cell transplantation). This review describes T-cell-associated changes during the evolution of multiple myelo-ma and provides an overview of T-cell-dependent immunooncology approaches under investigation. Vaccine and checkpoint inhibitor interventions are being explored across the multiple myeloma disease continuum; treatment modalities that redirect patient T cells to elicit an anti-multiple myeloma response, namely, chimeric antigen receptor (CAR) T cells and bispecific antibodies [including BiTE (bispecific T-cell engager) molecules], have been primarily evaluated to date in the relapsed and/or refractory disease setting. CAR T cells and bispecific antibodies/antibody constructs directed against B-cell maturation antigen have generated excitement, with clinical data demonstrating deep responses. An increased understanding of the complex interplay between the immune system and multiple myeloma throughout the disease course will aid in maximizing the potential for T-cell-dependent immuno-oncology strategies in multiple myeloma.

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Section: Vaccinesmentioning

confidence: 99%

Section: Vaccinesmentioning

confidence: 99%

How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma

Cohen

Raje

Fowler

et al. 2020

Clinical Cancer Research

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“…After tumor cell transplantation, tumor growth and immune responses in the mice were observed at regular intervals. Treatment was administered twice in a 7-day interval when the tumor volume reached 100 to 120 mm 3 . Within 2 weeks after the third immunization, the tumor volumes in each group were examined, and tumor inhibition rates were calculated.…”

Section: Immune Reconstitution and Multiple Myeloma Cell Transplantatmentioning

confidence: 99%

“…The current therapies include conventional chemotherapy, autologous stem cell transplantation, proteasome inhibitors (bortezomib), and immunomodulatory drugs (IMiD), such as thalidomide and lenalidomide. However, multiple myeloma remains difficult to cure, and novel therapies are urgently needed (3,4). Although immunotherapy has demonstrated good potential in cancer, this approach is suboptimal in multiple myeloma and requires further evaluation (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Lenalidomide Augments the Antitumor Activities of Eps8 Peptide-Specific Cytotoxic T Lymphocytes against Multiple Myeloma

Xie

Chen

et al. 2019

Molecular Cancer Therapeutics

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Cancer immunotherapy is a promising new approach to cancer treatment. It has been demonstrated that a high number of tumor-specific cytotoxic T cells (CTL) is associated with increased survival in patients with multiple myeloma. Here, we focused on EGFR pathway substrate 8 (Eps8) as a candidate tumor-associated antigen (TAA) in multiple myeloma. Previous work has shown that Eps8-based immunotherapy in HLA-A2 þ cancer patients may result in efficient antitumor immune responses against diverse tumor types. To improve immunotherapy for patients with multiple myeloma, we constructed a cocktail vaccine by combining several HLA-A2-restricted epitopes derived from Eps8 (Eps8 cocktail), including Eps8 101-2L (WLQDMILQV), Eps8 276-1Y9V (YLDDIEFFV), and Eps8 455-1Y (YLAESVANV). The CTLs induced by Eps8 cocktail (Eps8 cocktail-CTLs) showed highly effective anti-multiple myeloma activity, including Th1 cytokines production, cell proliferation, and cytotoxicity against HLA-A2 þ multiple myeloma cells. This study highlights the importance of using a cocktail vaccine instead of a single-peptide vaccine to induce a robust response. Importantly, we revealed that lenalidomide effectively stimulated the antitumor activity of the Eps8 cocktail-CTLs, with increasing expression trends for T-cell markers (CD28, CD40L, 41BB, and OX40). Compared with unstimulated CTLs and Eps8 cocktail-CTLs, lenalidomide-treated Eps8 cocktail-CTLs showed superior anti-multiple myeloma activity in humanized multiple myeloma models, including delaying tumor burden increases due to enhanced immune function. These results provide the framework for an Eps8 cocktail vaccination therapy to induce effective Eps8-specific CTLs in HLA-A2 þ patients with multiple myeloma. Moreover, these studies further demonstrate that lenalidomide augments the immune response, providing a possibility for its use in combination with peptide vaccines to improve patient outcomes.

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“…Finally, as treatment options in multiple myeloma continue to emerge, one of the most promising class of agents are immunotherapeutic approaches, including monoclonal antibodies, adoptive T-cell therapy, vaccines, and combination therapy. 65 Intravenous daratumumab is the first-in-class human monoclonal antibody against CD38 available for use in patients with RRMM. 66 Despite therapeutic advances, disease relapse is inevitable and multiple myeloma remains substantially incurable.…”

mentioning

confidence: 99%

A historical perspective on milestones in multiple myeloma research

Ribatti

2017

European J of Haematology

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The first well-documented case of multiple myeloma was reported in 1844 by Samuel Solly. In this article, the author presents a historical review of the disease. In particular, the review is focused on the main steps, including the definition of Bence Jones proteinuria, the characterization of tumoral plasma cells and serum globulins, and the fundamental contribution of Jan Waldenstrom. Finally, treatment of multiple myeloma, as well as the development of new agents, is discussed.

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Advances in immunotherapy in multiple myeloma

Abstract: Immunotherapeutic approaches have remarkably changed the treatment paradigm for multiple myeloma, and encouraging patient responses have warranted further investigation into mAbs, adoptive T-cell therapy, vaccines, and combination therapy.

Cited by 14 publications

References 67 publications

How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma

How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma

Lenalidomide Augments the Antitumor Activities of Eps8 Peptide-Specific Cytotoxic T Lymphocytes against Multiple Myeloma

A historical perspective on milestones in multiple myeloma research

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