Combining MPDL3280A with adoptive cell immunotherapy exerts better antitumor effects against cervical cancer

Abstract

As the second most common gynecologic malignant tumors with a high mortality rate, cervical cancer jeopardizes women's life worldwide. The low cure rate in cervical cancer patients is mainly attributed to the lack of effective therapies. One feasible novel strategy is to develop immunebased approaches such as adoptive cell immunotherapy of DCCIKs which represents a promising nontoxic antineoplastic immunotherapy preferred in clinic practice. However, the therapeutic effect is not as efficient as anticipated. Possible explanations are tumors exploit immunoregulatory checkpoints such as programmed death 1(PD1)/PDL1 which provides tumor cells an escape strategy of circumventing immunologic rejection from immune surveillance by hampering activated tumorspecific T cell activities and rendering them functionally exhausted. With reduced transformation activity and enhanced antigenicity, a modified HPV16 E7 (HPV16mE7) was used to load DCs with silenced SOCS1 mediated by a recombinant adenovirus to improve the targetability and efficiency against cervical cancer. Combined with anti-PDL1 antibody MPDL3280A therapy, the co-cultured DCCIKs were transfused into murine models bearing tumor of HPV16 E6/E7 expressing CaSki cells for in vitro/in vivo antitumor activity assay. Although all of the animals succumbed to CaSki tumors even after adoptive DCCIKs transfer or MPDL3280A immunotherapy, the infusion of PDL1 blocking monoclonal antibody with activated T cells cured 40% of animals. These data support PDL1 blockade improves the efficacy of adoptive DCCIKs therapy, providing a new approach of immunotherapy against cervical cancer.

Comprehensive Analysis of Monocarboxylate Transporter 4 (MCT4) expression in breast cancer prognosis and immune infiltration via integrated bioinformatics analysis

“…In recent years, breakthroughs in the field of immunotherapy have provided new approaches for BC treatment [ 2 , 3 ]. Programmed death ligand 1 (PD-L1) [ 4 ] interacting with Programmed cell death 1 (PD1) to induce an immunosuppressive effect [ 5 ] has been the focus of immunotherapy. The Food and Drug Administration (FDA) has granted approval of PD-L1 inhibitor atezolizumab when combined with nanoparticle albumin-bound (nab)-paclitaxel for unresectable locally advanced or metastatic triple negative breast cancer (TNBC) [ 6 ], based on the results of the IMpassion130 trial [ 7 , 8 ].…”

Activation of cytotoxic T lymphocytes by self-differentiated myeloid-derived dendritic cells for killing breast cancer cells expressing folate receptor alpha protein

“…This personalized approach uses the patient’s own immune cells to fight against cancer cells. These effector immune cells are either genetically modified or activated ex vivo , and after expansion, they are reinfused into the patient to eliminate cancer cells [ 8 , 9 ]. Cancer-specific cytotoxic T lymphocytes (CTLs) function upon recognition of tumor-associated antigens (TAAs) presented on cancer cells.…”

Suppression of phosphoinositide 3‐kinase/phosphoinositide‐dependent kinase‐1/serum and glucocorticoid‐induced protein kinase pathway

“…Cervical cancer is the third most common gynecologic malignancy worldwide (Waldmann, Eisemann, & Katalinic, 2013; Y. Zheng et al, 2017). Though chemical agents have been used to prevent cancer in high‐risk populations (Zou et al, 2005), the number of anticancer agents is limited due to their toxicity and chemoresistance (Lippman, Lee, & Sabichi, 1998; Zou et al, 2005).…”