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Clinical translation of cell therapies requires strategies that can manufacture cells efficiently and economically. One promising way to reproducibly expand T cells for cancer therapy is by attaching the stimuli for T cells onto artificial substrates with high surface area. Here, we show that a carbon nanotube-polymer composite can act as an artificial antigen-presenting cell to efficiently expand the number of T cells isolated from mice. We attach antigens onto bundled carbon nanotubes and combined this complex with polymer nanoparticles containing magnetite and the T-cell growth factor interleukin-2 (IL-2). The number of T cells obtained was comparable to clinical standards using a thousand-fold less soluble IL-2. T cells obtained from this expansion were able to delay tumour growth in a murine model for melanoma. Our results show that this composite is a useful platform for generating large numbers of cytotoxic T cells for cancer immunotherapy.

Objective To explore the role of immune dysregulation in antibiotic-refractory Lyme arthritis, the phenotype, frequency and function of CD4+ Teff and Treg cells were compared in patients with antibiotic-responsive or antibiotic-refractory arthritis. In the latter condition, infection-induced autoimmunity is thought to have a pathogenic role. Methods Matched peripheral blood (PB) and synovial fluid (SF) samples from 15 patients with antibiotic-responsive arthritis were compared with those from 16 patients with antibiotic-refractory arthritis using flow cytometry, suppression and cytokine assays. Results Critical differences between the 2 patient groups were found in the SF CD4+CD25hi+ populations, a subset of cells usually composed of FOXP3-positive Treg cells. In patients with antibiotic-refractory arthritis, this cell population often had fewer FOXP3-positive cells, and greater frequencies of FOXP3-negative (Teff) compared to patients with antibiotic-responsive arthritis. Moreover, in the refractory group, CD4+CD25hi+ cells had significantly greater expression of GITR and OX-40, two co-receptors that augment T cell function. Suppression assays showed that CD4+CD25hi+ cells in patients with refractory arthritis did not effectively suppress proliferation of CD4+CD25− cells, or secretion of IFN-γ or TNF-α, whereas those from patients with responsive arthritis did. Finally, in the refractory group, higher ratios of CD25hi+FOXP3−/CD25hi+FOXP3+ cells correlated directly with longer post-treatment durations of arthritis. Conclusion Patients with antibiotic-refractory Lyme arthritis often had lower frequencies of Treg, higher expression of activation co-receptors, and less effective inhibition of pro-inflammatory cytokines. This suggests that immune responses in these patients were excessively amplified leading to immune dysregulation and refractory arthritis.

The mechanisms whereby immune therapies affect progression of Type 1 diabetes (T1D) are not well understood. Teplizumab, an FcR non-binding anti-CD3 mAb, has shown efficacy in multiple randomized clinical trials. We previously reported an increase in the frequency of circulating CD8+ central memory (CD8CM) T cells in clinical responders, but the generalizability of this finding and the molecular effects of teplizumab on these T cells have not been evaluated. We analyzed data from 2 randomized clinical studies of teplizumab in patients with new and recent onset T1D. At the conclusion of therapy clinical responders showed a significant reduction in circulating CD4+ effector memory (CD4EM) T cells. Afterwards, there was an increase in the frequency and absolute number of CD8CM T cells. In vitro, teplizumab expanded CD8CM T cells by proliferation and conversion of non-CM T cells. Nanostring analysis of gene expression of CD8CM T cells from responders and non-responders vs placebo-treated control subjects identified decreases in expression of genes associated with immune activation and increases in expression of genes associated with T cell differentiation and regulation. We conclude that CD8CM T cells with decreased activation and regulatory gene expression are associated with clinical responses to teplizumab in patients with T1D.