Trial watch: Tumor-targeting monoclonal antibodies for oncological indications

Abstract

An expanding panel of monoclonal antibodies (mAbs) that specifically target malignant cells or intercept trophic factors delivered by the tumor stroma is now available for cancer therapy. These mAbs can exert direct antiproliferative/cytotoxic effects as they inhibit pro-survival signal transduction cascades or activate lethal receptors at the plasma membrane of cancer cells, they can opsonize neoplastic cells to initiate a tumor-targeting immune response, or they can be harnessed to specifically deliver toxins or radionuclides to transformed cells. As an indication of the success of this immunotherapeutic paradigm, international regulatory agencies approve new tumor-targeting mAbs for use in cancer patients every year. Moreover, the list of indications for previously licensed molecules is frequently expanded to other neoplastic disorders as the results of large, randomized clinical trials become available. Here, we discuss recent advances in the preclinical and clinical development of tumor-targeting mAbs for oncological indications.

Keywords: 5-fluorouracil; ADCC; Food and Drug Administration; FOLFIRI; acute lymphocytic leukemia; AML; acute myeloid leukemia; BiTE; anaplastic large-cell lymphoma; ALL; antibody-dependent cell-mediated cytotoxicity; ALCL; bevacizumab; bispecific T-cell engager; CDC; cetuximab; chronic lymphocytic leukemia; CRC; coagulation factor III; FDA; colorectal carcinoma; DLBCL; complement-dependent cytotoxicity; CLL; diffuse large B-cell lymphoma; EGFR; epidermal growth factor receptor; F3; folinic acid; hepatocellular carcinoma; HHV-8; human herpesvirus-8; IL; interleukin; mAb; irinotecan; FOLFOX; mantle cell lymphoma; MDS; monoclonal antibody; MMAE; monomethyl auristatin E; MCL; myelodysplastic syndrome; NHL; non-Hodgkin's lymphoma; NSCLC; non-small cell lung carcinoma; ORR; obinutuzumab; overall response rate; OS; overall survival; PFS; oxaliplatin; HCC; phosphoinositide-3-kinase; RCC; progression-free survival; PI3K; ramucirumab; renal cell carcinoma; SLL; rituximab; small lymphocytic leukemia; TAA; trastuzumab; tumor-associated antigen.