Strategies to Endow Cytotoxic T Lymphocytes or Natural Killer Cells with Antibody Activity against Carcinoembryonic Antigen

Abstract

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are main effecter cells in cellular immunity against tumor cells. T-cell immunotherapy is based on the assumption that tumor(-associated) antigen (TA) peptides are correctly presented by HLA class I molecules on target tumor cells, and NK cell immunotherapy is based on the hypothesis that cell surface TAs or ligands for NK receptors are widely expressed in tumor cells. However, human tumor cells often lose HLA class I molecules, and target cell ligands for NK receptors are not always expressed in human tumor cells. These altered HLA class I phenotypes and non-ubiquitous expression of NK receptor ligands constitute the major tumor escape mechanism facing tumor-specific CTL and/or NK cell mediated responses. These facts also indicate that it is not easy to eliminate the target tumors only by activating tumor-specific CTLs or NK cells with cancer vaccine treatments. On the other hand, it is easily confirmed by immunohistochemistry whether or not antibody-recognized TAs exist on the cell surface of target tumor cells. Therefore, endowing CTLs or NK cells with antigen-binding specificity of anti-TA antibody is a promising approach for re-targeting the activities of these effector cells to tumor cells in an HLA-independent manner. This review summarizes the following four new strategies for re-targeting CTLs or NK cells to carcinoembryonic-antigen-expressing tumor cells: (1) bispecific antibody technology; (2) antibody-cytokine fusion protein technology; (3) chimeric immune receptor technology, and (4) antibody-HLA/peptide complex technology.

Tumor Growth Suppression of Pancreatic Cancer Orthotopic Xenograft Model by CEA-Targeting CAR-T Cells

“…The scFv of the monoclonal antibody F11-39 specific to CEA in the VL-VH orientation [16], along with a CD8a hinge, CD28 transmembrane domain and CD3ζ signaling domains, and GITR intracellular domain, were cloned into a pMS3 retroviral vector [17]. GITR plays a functional role in regulating the activity of regulatory T cells through GITR ligands [18].…”

Engineered Multifunctional Nano‐ and Biological Materials for Cancer Immunotherapy

“…Another single domain antibody was designed [ 143 ] to target carcinoembryonic antigen (CEA) derived from natural camel heavy‐chain only antibodies (HCAbs) that do not consist of any light chains and do not have a CH1 domain. CEA is expressed in GI, pancreatic, lung, and breast cancers and not in healthy tissues, [ 160 ] making this a widely applicable target for cancer immunotherapy. Here a BiSS (bispecific antibody with a single domain, single‐domain antibodies) antibody was constructed by targeting CD16 and CEA through expression and produced in Escherichia coli .…”