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

Abstract

A subpopulation of patients with HNSCC who are nonresponders to alphaCD3 stimulation has been identified, showing reduced proliferation and IL-12 and IFN-gamma secretion. Nonresponders stimulated with alphaCD3/alphaCD28 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.

CD3/CD28-costimulated T1 and T2 subsets: differential in vivo allosensitization generates distinct GVT and GVHD effects

“…5,6 We found that CD3/CD28 costimulation under T1-or T2-promoting conditions yielded greatly increased T-cell expansion compared with CD3 stimulation alone; this result is consistent with the known antiapoptotic role of CD28 signaling to sustain proliferation possibly through the up-regulation of bcl-x L 8 or other molecules. 27 Our finding that CD8 ϩ T cells expanded more than CD4 ϩ T cells under T1 and T2 culture conditions is consistent with the known role of CD28 in CD4 and CD8 activation and the increased capacity of CD8 ϩ T cells to proliferate.…”

“…1,2 The use of CD3/CD28-generated T cells has been evaluated as a methodology for the cellular immunotherapy of cancer 3 and immuno-augmentation in patients with HIV infection. [4][5][6] The potential application of this approach may reside in the usefulness of CD28 costimulation to promote the generation of a polyclonal T cell receptor repertoire 7 with enhanced effector function. [8][9][10] The successful application of this CD28-based immunotherapy approach will likely require the generation of antigen specificity, either through further in vitro culture or in vivo sensitization.…”

Retrovirus-mediated gene transfer in primary T lymphocytes impairs their anti–Epstein-Barr virus potential through both culture-dependent and selection process–dependent mechanisms

“…However, we have previously demonstrated that replacing the initial CD3/IL-2-induced activation by CD3/CD28 mAb-coated beads and IL-2 could prevent the occurrence of TCRBV repertoire alterations. 18 Moreover, CD28 costimulation has been shown to reverse CD3 unresponsiveness 19 and to exert antiapoptotic effects. 20-22 Thus, we tested whether an initial activation by CD3/CD28 beads and IL-2 …”

Incomplete Th2 skewing of cytokines in plasma of patients with squamous cell carcinoma of the head and neck

“…Head and neck squamous cell carcinomas (HNSCC) patients are particularly deficient in their immune responsiveness. In one study, T cells from about one-third of HNSCC patients were reported to be unresponsive to stimulation through CD3 [6]. Mitogen-stimulated proliferation by T cells from HNSCC patients diminished with more progressive disease, and decreased T-cell blastogenesis was associated with reduced patient survival [1].…”