Anti-CD3/Anti-CD28 Bead Stimulation Overcomes CD3 Unresponsiveness in Patients With Head and Neck Squamous Cell Carcinoma

• Published in: Archives of otolaryngology--head & neck surgery Vol. 126; no. 4; pp. 473 - 479
• Main Authors: Shibuya, Terry Y, Wei, Wei-Zen, Zormeier, Michelle, Ensley, John, Sakr, Wael, Mathog, Robert H, Meleca, Robert J, Yoo, George H, June, Carl H, Levine, Bruce L, Lum, Lawrence G
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 01.04.2000
• Subjects: Antibodies, Monoclonal; Biological and medical sciences; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - therapy; CD28 Antigens - immunology; CD3 Complex - immunology; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - therapy; Humans; Immune Tolerance - immunology; Immunopathology; Immunotherapy; Immunotherapy (general aspects); In Vitro Techniques; Interferon-gamma - immunology; Interleukin-12 - immunology; Lymphocyte Activation - immunology; Medical sciences; Middle Aged; Otorhinolaryngology. Stomatology; T-Lymphocytes - immunology; Tumors; Human; Squamous cell carcinoma; Immune response; Lymph node; Induction; Treatment efficiency; Stimulation; Malignant tumor; Monoclonal antibody; Immunology; Mononuclear cell; Immunotherapy; T-Lymphocyte; Head and neck; ENT disease; Adult; Comparative study; Responder
• ISSN: 0886-4470; 2168-6181; 1538-361X; 2168-619X
• DOI: 10.1001/archotol.126.4.473

OBJECTIVES To test whether T-cell CD3 responses are altered in patients with advanced-stage head and neck squamous cell carcinoma (HNSCC) and whether anti-CD3/anti-CD28 (αCD3/αCD28) bead stimulation could reverse CD3 unresponsiveness. DESIGN Anti-CD3 (αCD3) monoclonal antibody immobilized on tissue culture plastic was used to stimulate lymph node mononuclear cells (LNMCs) and peripheral blood mononuclear cells (PBMCs) from patients with advanced-stage HNSCC. Proliferation, T-cell phenotype, and cytokines were measured during 8-day in vitro stimulation. Immune-enhancing properties of αCD3/αCD28 beads were also tested on LNMCs and PBMCs. Cytotoxicity of bead-activated T cells (ATCs) was measured against autologous and allogeneic HNSCC. RESULTS Six patients were nonresponders to αCD3 stimulation defined by tritium (3H) incorporation of less than 3500 cpm, whereas 11 patients were responders with 3H incorporation of 3500 cpm or more. Responders produced higher levels of interleukin (IL)–12 and interferon γ (IFN-γ) after αCD3 stimulation than nonresponders. No phenotypic or clinical differences were identified between groups. Stimulation with αCD3/αCD28 beads enhanced IFN-γ and IL-2 produced by both groups. Bead ATCs were generated from PBMCs of patient 11 in the responder group and lysed (± SD) 100% ± 1% of autologous tumor and 49% ± 1% of allogeneic tumor. Bead ATCs from LNMCs of this patient lysed 58% ± 1% of autologous tumor and 63% ± 1% of allogeneic tumor. CONCLUSIONS A subpopulation of patients with HNSCC who are nonresponders to αCD3 stimulation has been identified, showing reduced proliferation and IL-12 and IFN-γ secretion. Nonresponders stimulated with αCD3/αCD28 beads reversed immune unresponsiveness and induced a type 1 cytokine response. Bead-generated ATCs from patient 11 in the responder group lysed autologous and allogeneic HNSCC in vitro, suggesting a possible effective immunotherapeutic modality in the treatment of HNSCC.Arch Otolaryngol Head Neck Surg. 2000;126:473-479-->