title: Tumor antigen-specific monoclonal antibodies and induction of T-cell immunity.
abstract: For decades the primary available cancer therapies were relatively nonspecific cytotoxic agents which, while effective in some patients, were limited by narrow therapeutic indices, extensive toxicity and development of resistance, likely due to tumor heterogeneity. Although these chemotherapies remain common tools of conventional treatment, the approval of a growing number of tumor antigen (TA)-specific monoclonal antibodies (mAbs) by the US Food and Drug Administration has driven a shift in the paradigm of cancer therapy. For a subset of patients with lymphoma, colorectal, head and neck, and breast cancers, the inclusion of rituximab (anti-CD20), cetuximab (anti-human epidermal growth factor 1), and trastuzumab (anti-human epidermal growth factor 2) has resulted in overall improved clinical response rates and survival advantages. The mechanisms that contribute to these effects are limited not only to inhibition of signaling pathways but also include cell-mediated cytotoxicity by innate immune cells and priming of effector cells of adoptive immunity triggered by the TA-specific mAb. However, as the use of these therapeutic mAbs has become more widespread, it has been observed that there is significant variability of response in patients treated with these agents. Thus, the factors that mediate this variability in clinical responses must be elucidated to optimize the use of TA-specific mAbs.
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Sumita
authors.initials: S
authors.lastname: Trivedi
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Hyun-Bae
authors.initials: HB
authors.lastname: Jie
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA; Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA. Electronic address: ferrrl@upmc.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D006801:Humans; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm