[PMID]: | 29223828 |
[Au] Autor: | Ferris RL; Lenz HJ; Trotta AM; García-Foncillas J; Schulten J; Audhuy F; Merlano M; Milano G |
[Ad] Endereço: | Department of Otolaryngology, University of Pittsburgh Cancer Institute, University of Pittsburgh, 5117 Centre Avenue, Suite 2.26, Pittsburgh, PA 15213, United States. Electronic address: ferrrl@UPMC.EDU. |
[Ti] Título: | Rationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors: Harnessing innate and adaptive immunity through IgG1 isotype immune effector stimulation. |
[So] Source: | Cancer Treat Rev;63:48-60, 2018 Feb. |
[Is] ISSN: | 1532-1967 |
[Cp] País de publicação: | Netherlands |
[La] Idioma: | eng |
[Ab] Resumo: | Immunoglobulin (Ig) G1 antibodies stimulate antibody-dependent cell-mediated cytotoxicity (ADCC). Cetuximab, an IgG1 isotype monoclonal antibody, is a standard-of-care treatment for locally advanced and recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and metastatic colorectal cancer (CRC). Here we review evidence regarding the clinical relevance of cetuximab-mediated ADCC and other immune functions and provide a biological rationale concerning why this property positions cetuximab as an ideal partner for immune checkpoint inhibitors (ICIs) and other emerging immunotherapies. We performed a nonsystematic review of available preclinical and clinical data involving cetuximab-mediated immune activity and combination approaches of cetuximab with other immunotherapies, including ICIs, in SCCHN and CRC. Indeed, cetuximab mediates ADCC activity in the intratumoral space and primes adaptive and innate cellular immunity. However, counterregulatory mechanisms may lead to immunosuppressive feedback loops. Accordingly, there is a strong rationale for combining ICIs with cetuximab for the treatment of advanced tumors, as targeting CTLA-4, PD-1, and PD-L1 can ostensibly overcome these immunosuppressive counter-mechanisms in the tumor microenvironment. Moreover, combining ICIs (or other immunotherapies) with cetuximab is a promising strategy for boosting immune response and enhancing response rates and durability of response. Cetuximab immune activity-including, but not limited to, ADCC-provides a strong rationale for its combination with ICIs or other immunotherapies to synergistically and fully mobilize the adaptive and innate immunity against tumor cells. Ongoing prospective studies will evaluate the clinical effect of these combination regimens and their immune effect in CRC and SCCHN and in other indications. |
[Mh] Termos MeSH primário: |
Imunidade Adaptativa/imunologia Citotoxicidade Celular Dependente de Anticorpos/imunologia Antineoplásicos Imunológicos/imunologia Cetuximab/imunologia Imunidade Inata/imunologia Imunoglobulina G/imunologia Neoplasias/imunologia
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[Mh] Termos MeSH secundário: |
Antineoplásicos Imunológicos/uso terapêutico Cetuximab/uso terapêutico Quimioterapia Combinada/métodos Seres Humanos Imunoterapia/métodos Neoplasias/terapia
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; REVIEW |
[Nm] Nome de substância:
| 0 (Antineoplastic Agents, Immunological); 0 (Immunoglobulin G); PQX0D8J21J (Cetuximab) |
[Em] Mês de entrada: | 1802 |
[Cu] Atualização por classe: | 180209 |
[Lr] Data última revisão:
| 180209 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 171211 |
[St] Status: | MEDLINE |
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