The status,limitation and improvement of adoptive cellular immunotherapy in advanced urologic malignancies

In recent years, immunotherapy has been gradually established as the fourth frequently adopted antitumor therapy, following surgery, chemotherapy and radiotherapy, for advanced urologic malignancies with an improved understanding of theoretical basis, such as molecular biology and immunology. Thereinto, adoptive cellular immunotherapy （ACI） has become one of the hotspots, which comprises a variety of treatment approaches, such as TIL, CIK cell, ~＇~ T cell, CAR-engineered T cell and Allogeneie stem cell transplantation （alloSCT）. Although preclinical efficacy has been demonstrated remarkably, clinical trials could not consistently show the benefit due to multi-factors in complex immnnosuppressive microenvironment in vivo compared to that of in vitro. Here we review some timely aspects of ACI for advanced urologic malignancies, and describe the current status and limitation of immunotherapy from the cellular level. It＇s our expectation to provide prompting consideration of novel combinatorial ACI strategies and a resurgence of interest in ACI for advanced urologic malignancies.

Advancements in adoptive CAR immune cell immunotherapy synergistically combined with multimodal approaches for tumor treatment

Adoptive immunotherapy,notably involving chimeric antigen receptor(CAR)-T cells,has obtained Food and Drug Administration(FDA)approval as a treatment for various hematological malignancies,demonstrating promising preclinical efficacy against cancers.However,the intricate and resource-intensive autologous cell processing,encompassing collection,expansion,engineering,isolation,and administration,hamper the efficacy of this therapeutic modality.Furthermore,conventional CAR T therapy is presently confined to addressing solid tumors due to impediments posed by physical barriers,the potential for cytokine release syndrome,and cellular exhaustion induced by the immunosuppressive and heterogeneous tumor microenvironment.Consequently,a strategic integration of adoptive immunotherapy with synergistic multimodal treatments,such as chemotherapy,radiotherapy,and vaccine therapy etc.,emerges as a pivotal approach to surmount these inherent challenges.This collaborative strategy holds the key to addressing the limitations delineated above,thereby facilitating the realization of more precise personalized therapies characterized by heightened therapeutic efficacy.Such synergistic strategy not only serves to mitigate the constraints associated with adoptive immunotherapy but also fosters enhanced clinical applicability,thereby advancing the frontiers of therapeutic precision and effectiveness.

The clinical effects of DC-CIK cells combined with chemotherapy in the treatment of advanced NSCLC

Objective: The aim of the study was to evaluate the safety and therapeutic effects of autologous dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) combined with chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Methods: Fifty patients with advanced NSCLC (stages III to IV), who had received therapies in our Center (Department of Biotherapy, Affiliated to Cancer Hospital of Shanxi Medical University, Taiyuan, China) from August 2008 to January 2010, were treated by DC-CIK + chemotherapy as the combined treatment group; fifty advanced NSCLC patients treated with chemotherapy at the same time served as controls. The immunologic function, short-term therapeutic effects, the 1-year survival rate, the life quality, the chemotherapy side effects were compared between the two groups, the safety and therapeutic effects of DC-CIK cells therapy were observed too. Results: There was no obvious change of subsets of T cells in peripheral blood before and after therapy in DC-CIK + chemotherapy group, and IFN-γ was improved after therapy in this group (P < 0.05); in chemotherapy alone group, the ratios of CD3+CD4+, CD3+CD8+, CD3-CD56+ cells and the secretion of IL-2, TNF-α decreased significantly after therapy (P < 0.05); the ratios of CD3+CD8+, CD3+CD56+ were improved after cell culture (P < 0.05). The disease control rate (DCR) of DC-CIK + chemotherapy group was higher than that in the chemotherapy alone group (78.0% vs 56.0%, P < 0.05); the 1-year survival rates of DC-CIK + chemotherapy group and chemotherapy alone group were 50% and 44% respectively, had no significant difference. Compared with chemotherapy alone group, the occurrence of chemotherapy side effects (including bone marrow suppression, nausea and vomiting, peripheral nerve toxicity) was less in the DC-CIK + chemotherapy group (P < 0.05). The physical and appetite were better in DC-CIK + chemotherapy group after therapy. Conclusion: To compare with simple chemotherapy, DC-CIK + chemotherapy for advanced NSCLC is safe and effective, and it can improve patients' life quality and remission rate, and prolong their survival time.