Idiotype vaccination using dendritic cells after autologous peripheral blood progenitor cell transplantation for multiple myeloma

Liso, Arcangelo; Stockerl-Goldstein, Keith; Auffermann-Gretzinger, Susanne; Benike, Claudia; Reichardt, Volker L.; Beckhoven, Adrienne van; Rajapaksa, Ranjani; Engleman, Edgar G.; Blume, Karl G.; Levy, Ronald

doi:10.1016/s1083-8791(00)70027-9

Cited by 135 publications

(70 citation statements)

References 27 publications

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“…The two patients that developed cellular IR also were in CR after auto-HCT (before vaccination) and they remained in CR at the time of the publication of the report; therefore, the clinical impact of this approach remains to be determined. A larger series of a total of 26 patients had similar results, 59 and other Id-based strategies are under investigation. 60 Rosenblatt et al 61 used DC/PCM cell fusions in the early postauto-HCT setting as additional consolidation.…”

Section: Myeloma Vaccinesmentioning

confidence: 82%

Beyond consolidation: auto-SCT and immunotherapy for plasma cell myeloma

Lendvai

Cohen

Cho

2015

Bone Marrow Transplant

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Autologous hematopoietic cell transplantation (auto-HCT) is the standard consolidation therapy for plasma cell myeloma patients following induction therapy. Auto-HCT improves disease-free survival (DFS), but is generally not curative. The allogeneic HCT experience demonstrated that T-cell immunotherapy can confer long-term DFS. Preclinical and clinical data indicate that myelomaassociated Ags elicit humoral and cellular immune responses (IRs) in myeloma patients. These findings strongly suggest that the immunotherapeutic strategies, including immune checkpoint inhibitors, therapeutic cancer vaccines and adoptive cellular therapies, are promising avenues of clinical research that may be most applicable in the minimal residual disease state following auto-HCT. These strategies are designed to prime or augment antimyeloma IRs and promote a 'host-vs-myeloma' effect that may result in durable DFS. Innovative clinical trials investigating immune checkpoint inhibitors and cancer vaccines have demonstrated that robust immunity against myeloma-associated Ags can be elicited in the setting of auto-HCT. A diverse array of immunotherapeutic strategies have entered clinical trials in myeloma, including PD-1/PD-L1 inhibitors, DC/myeloma cell fusion vaccines and adoptive chimeric Ag receptor T-cell therapy, and further investigation of combinations of immunologic and pharmaceutical agents are expected in the near future. In this review, we will discuss the preclinical data supporting immunotherapy in auto-HCT for myeloma, clinical investigation of these strategies and the future prospects of immunotherapy in pursuit of the goal of curative therapy.

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Section: Myeloma Vaccinesmentioning

confidence: 82%

Beyond consolidation: auto-SCT and immunotherapy for plasma cell myeloma

Lendvai

Cohen

Cho

2015

Bone Marrow Transplant

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“…40,[225][226][227] In some studies, patients also received soluble antigen, 40 complicating evaluation of the response to the idiotype-pulsed DCs. Occasional tumor regressions were observed in some patients with lymphoma.…”

Section: Lymphoma and Myelomamentioning

confidence: 99%

Active immunization against cancer with dendritic cells: The near future

2001

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DCs 1 are antigen-presenting cells that regulate several components of the immune system. The mature or terminal stage of DC development induces specific T-cell immunity and resistance to experimental tumors in vivo. However, DC maturation is induced by inflammatory and microbial stimuli, so it is unlikely that mature DCs normally present antigens from tumor cells in cancer patients. Accordingly, clinical studies have begun in which DCs are generated ex vivo, charged with tumor antigens, exposed to maturation stimuli and reinfused to immunize patients. This approach has the potential to control responses to cancer antigens in a specific and nontoxic manner, in both vaccination and therapeutic settings.DCs can mobilize several immune resistance mechanisms. These include CD8ϩ CTLs, CD4 ϩ helper T cells, NK and NKT cells. Each of these lymphocytes recognizes targets through a distinct mechanism and has the capacity to kill tumor cells and release valuable protective cytokines like IFN-␥. CD4 ϩ T cells also provide essential help for the expansion and maintenance of CD8 ϩ cytolytic cells, while NK and NKT cells can eliminate targets that dampen presentation on MHC class I to escape CTL recognition. The stimulation and concerted action of these classes of lymphocytes can now be studied directly in patients, using ex vivo-derived DCs.Several findings have emerged from studies of healthy volunteers who have been immunized with DCs charged with model antigens, KLH protein and influenza virus matrix peptide. Mature DCs elicit a polarized Th1 type of CD4 T-cell response, only a single injection being required. Vaccination with antigen-bearing DCs also markedly improves the functional affinity of CD8 ϩ T cells. These findings are important in the context of immunotherapy because Th1 cells are more efficient helper cells in experimental models of viral infection and tumors, while high-affinity CTLs should improve recognition of tumor-derived peptides. An important caution also has surfaced when DCs are not adequately differentiated. Immature DCs can silence adaptive T-cell responses, e.g., by inducing IL-10 -producing, T-reg cells.DC-based active immunization does not result in major shortterm toxicity in healthy subjects or cancer patients. Tumor-specific T-cell responses have been induced and detected in fresh blood specimens without the need for restimulation in vitro. However, the immune responses observed in the first protocols are still smaller than those seen naturally in acute viral infections. Occasional clinical regressions have been noted in these initial feasibility studies, particularly in melanomas, pediatric tumors, lymphomas, prostate cancers and renal cell cancers. This information, coupled with progress in DC biology, suggests many ways to improve the efficacy of this new therapy. Some relevant topics include antigen loading and DC maturation procedures, frequency and route of DC injection, efficiency of DC homing to lymphoid tissues and their longevity once there and the role of distinct DC subsets. A val...

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“…Until now, the various studies of DC-based Id vaccination in MM have been reported (Bendandi et al, 2006;Lim & Bailey-Wood, 1999;Liso et al, 2000;Reichardt et al, 2003;Rollig et al, 2011;Titzer et al, 2000;Yi et al, 2002Yi et al, , 2010. Although Id-specific CTLs and immune response could be induced in some patients, clinical responses have been observed rarely in few patients after vaccination (Titzer et al, 2000).…”

Section: Idiotype and Idiotype-pulsed Dcs In MMmentioning

confidence: 99%