Cellular immunotherapy for plasma cell myeloma

Abstract

Allogeneic hematopoietic cell transplantation for plasma cell myeloma can lead to graft-vs-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies seek to induce more specific, reliable and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Strategies under development include infusion of vaccine-primed and ex vivo expanded/costimulated autologous T cells after high-dose melphalan, genetic engineering of autologous T cells with receptors for myeloma-specific epitopes, administration of DC/plasma cell fusions and administration expanded marrow-infiltrating lymphocytes. In addition, novel immunomodulatory drugs such as inhibitors of the programmed death-1 T cell regulatory pathway may synergize with cellular immunotherapies.

Immunotherapy for multiple myeloma: Current status and future directions

“…We and others showed that myeloma patients have high levels of circulating Tregs in their blood (Rosenblatt et al, 2013;Han et al, 2008;Garfall et al, 2013). Others have shown that high Tregs levels predict for early progression and poor outcome (Prabhala et al, 2006;Feyler et al, 2009;Braga et al, 2012;Giannopoulos et al, 2012;Muthu Raja et al, 2012;Rutella and Locatelli, 2012).…”

“…Allo-SCT has been shown to produce durable responses in MM patients who received grafts from HLA-matched sibling donors (Gahrton et al, 1991). It is, however, notorious for higher treatment-related toxicity, especially with myeloablative conditioning regimens which have been supplanted by reduced-intensity conditioning (RIC) regimens (Garfall et al, 2013). Despite the development of the latter, allo-SCT is still not routinely employed due to lack of survival advantage over standard ASCT (Lokhorst et al, 2010).…”

Vaccination of multiple myeloma: Current strategies and future prospects

“…Strategies under development include infusion of vaccineprimed and ex vivo expanded/costimulated autologous T cells after high-dose melphalan, genetic engineering of autologous T cells with receptors for myeloma-specific epitopes, administration of DC/plasma cell fusions and administration expanded marrow-infiltrating lymphocytes. In addition, novel immunomodulatory drugs may synergize with cellular immunotherapies [121].…”

Role of Immune Therapies for Myeloma

“…A potentially promising approach of obtaining myeloma-specific T cells for ex vivo manipulation and adoptive transfer involves the use of bone marrowinfiltrating cells (MILs). 46 These cells are thought to represent a polyclonal population of T cells reactive to myeloma-associated antigens but subject to tumorinduced anergy in the bone marrow microenvironment. In preclinical studies, bone marrow-derived lymphocytes have been shown to demonstrate greater proliferative response to ex vivo activation and expansion and greater myeloma-specific cytotoxicity compared with lymphocytes isolated from the peripheral blood.…”