Cellular and Vaccine-Based Immunotherapy for Hematologic Malignancies

Cellular immunotherapy has transformed clinical outcomes for patients with hematologic malignancies. Allogeneic transplantation represents a potent form of cellular-based immunotherapy mediated by alloreactive lymphocyte recognition of tumor cells via HLA disparity. However, the lack of specificity of this approach results in considerable risk for treatment-associated morbidity and mortality. Efforts to develop tumor-specific immunity have been propelled forward through the enhanced understanding of the complex interactions between malignancy and host immunity and the factors influencing the equilibrium between tolerance and activation. Cancer vaccines have been explored in an effort to induce expansion of tumor-reactive T cells through enhanced presentation of tumor-associated antigens. Immune response potentially correlates with protection from relapse but may not be effective in higher volume disease. Chimeric antigen receptor (CAR) T cells involve the ex vivo genetic manipulation of the effector cells to express a binding site to tumor-associated surface proteins, costimulatory signaling, and the T-cell receptor machinery. CAR T therapy has been associated with dramatic responses with durable remission in a subset of patients. An alternative approach involves the use of NK cell therapy harnessing the immunologic potency of adaptive immune mechanisms with the capacity for tumor specificity. Future directions have focused on elucidating the mechanisms of resistance, overcoming the immunosuppressive milieu of the tumor microenvironment, and combinatorial approaches.