Here we present an anti-CD3 loaded PLGA/ALG/CHI Mg micromotor systems, with degradable constituents and Mg-water reaction propulsion, thus ensuring a superior biocompatibility. Porous hydrogel formed by ALG/CHI offers high capacity of antigen loading, along with biocompatibility. By efficient loading of anti-human CD3 as an antigen and activating the calcium ion channel of Jurkat T cell, vital for immunotherapy, the motor system extends the application scope of micro/nanomotor systems from cargo (drug) delivery to interaction with the biointerface and immune activity modulation.
To investigate whether CD155 is an attractive target for T cell-mediated immunotherapy against human bladder cancer, we examined the novel bispecific antibody anti-CD3 x anti-CD155 (CD155Bi-Ab) for its ability to redirect activated T cells (ATCs) to target bladder cancer cells was examined. Expression of CD155 was detected by flow cytometry on the surface of bladder cancer cells, including T24 and Pumc-91 cells, and their chemotherapeutic drug-resistant counterparts. ATCs generated from healthy donors were stimulated with anti-CD3 monoclonal antibody, anti-CD28 monoclonal antibody and interleukin-2 (IL-2) for 14 days. The cytotoxic activity of ATCs armed with CD155Bi-Ab against bladder cancer cells was detected by LDH and luciferase quantitative assay. Furthermore, ATCs generated from bladder cancer patients were also armed with CD155Bi-Ab to verity the cell killing by the same methods. In contrast to unarmed ATCs, CD155Bi-armed ATCs against bladder cancer cells were increased cytotoxic activity at effector/target (E/T) ratios of 5:1, 10:1, and 20:1, with more IFN-γ, TNF-α secreting. It is worth noting that in spite of the presence of immunosuppression in bladder cancer patients and the drug resistance in chemotherapeutic drug-resistant cancer cell lines, not only the anti-tumor effect of CD155Bi-armed ATCs generated from bladder cancer patients still showed significantly but only higher level of activation marker CD69 was expressed. Taken together, our results suggest that CD155 is an effective target for the CD155-positive bladder cancer. And CD155Bi-Ab-armed ATCs are promisingly to provide a novel strategy for current CD155-positive bladder cancer therapy.
Photothermal immunotherapy, the combination of photothermal hyperthermia and immunotherapy, is a noninvasive and desirable therapeutic strategy to address the deficiency of traditional photothermal ablation for tumor treatment. However, insufficient T-cell activation following photothermal treatment is a bottleneck to achieve satisfactory therapeutic effectiveness. In this work, a multifunctional nanoplatform is rationally designed and engineered on the basis of polypyrrole-based magnetic nanomedicine modified by T-cell activators of anti-CD3 and anti-CD28 monoclonal antibodies, which have achieved robust near infrared laser-triggered photothermal ablation and long-lasting T-cell activation, realizing diagnostic imaging-guided immunosuppressive tumor microenvironment regulation following photothermal hyperthermia by reinvigorating tumor-infiltrating lymphocytes. By virtue of high-efficient immunogenic cell death and dendritic cell maturation combined with T-cell activation, this nanosystem markedly restrains primary and abscopal tumors as well as metastatic tumors with negligible side effects in vivo, exerting the specific function for suppressing tumor recurrence and metastasis by establishing a long-term memory immune response.
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