Adoptive immunotherapy for cancer: the next generation of gene‐engineered immune cells

Abstract

Adoptive cellular immunotherapy involving transfer of tumor-reactive T cells has shown some notable antitumor responses in a minority of cancer patients. In particular, transfer of tumor-infiltrating lymphocytes has resulted in long-term objective responses in patients with advanced melanoma. However, the inability to isolate sufficient numbers of tumor-specific T cells from most malignancies has restricted the broad utility of this approach. An emerging approach to circumvent this limitation involves the genetic modification of effector cells with T cell receptor (TCR) transgenes or chimeric single-chain variable fragment (scFv) receptors that can specifically redirect T cells to tumor. There has been much progress in the design of TCR and scFv receptors to enhance the antigen-specific activation of effector cells and their trafficking and persistence in vivo. Considerable effort has been directed toward improving the safety of this approach and reducing the immunogenicity of the receptor. This review discusses the latest developments in the field of adoptive immunotherapy using genetically modified immune cells that have been transduced with either TCR or scFv receptor transgenes and used in preclinical and clinical settings as anticancer agents.

Infusing CD19-Directed T Cells to Augment Disease Control in Patients Undergoing Autologous Hematopoietic Stem-Cell Transplantation for Advanced B-Lymphoid Malignancies

“…CARs are ''universal'' in that they bind TAAs independent of major histocompatibility complex (MHC), and thus one receptor construct can be used to treat a population of patients with the same TAA + tumors. Multiple CAR designs have emerged to dock with multiple TAAs and to provide a fully competent activation signal in desired T-cell subsets (Berry et al, 2009;June et al, 2009;Jena et al, 2010). CAR + T cells have been tested in multiple trials at multiple centers, as we have reviewed ( Jena et al, 2010).…”

Cytokine-induced killer cells for cell therapy of acute myeloid leukemia: improvement of their immune activity by expression of CD33-specific chimeric receptors

“…The so-called 'third-generation' CAR might conceivably represent optimal constructs, as also recently shown in in vivo tumor models. 20 With this study we aimed at improving CIK cell activity against AML through the genetic modification of the cells with two different CAR specific for the CD33 myeloid antigen, containing the ζ or the CD28-OX40-ζ signaling domain.…”

Nanobody, New Agent for Combating Against Breast Cancer Cells

“…However, despite encouraging responses in patients with melanoma, response rates for several cancers such as breast cancer have remained low. This is partly because of the difficulty in isolating, expanding low frequent endogenous tumourreactive T cells and their poor persistence after transfer (Berry et al, 2009;Hawkins et al, 2010). Meanwhile, tumours deploy strategies to persist and proliferate even if a large numbers of tumour-specific T cells exist.…”