Dataset Information

Killers at the crossroads: The use of innate immune cells in adoptive cellular therapy of cancer.

ABSTRACT: Adoptive cell therapy (ACT) is an approach to cancer treatment that involves the use of antitumor immune cells to target residual disease in patients after completion of chemo/radiotherapy. ACT has several advantages compared with other approaches in cancer immunotherapy, including the ability to specifically expand effector cells in vitro before selection for adoptive transfer, as well as the opportunity for host manipulation in order to enhance the ability of transferred cells to recognize and kill established tumors. One of the main challenges to the success of ACT in cancer clinical trials is the identification and generation of antitumor effector cells with high avidity for tumor recognition. Natural killer (NK) cells, cytokine-induced killers and natural killer T cells are key innate or innate-like effector cells in cancer immunosurveillance that act at the interface between innate and adaptive immunity, to have a greater influence over immune responses to cancer. In this review, we discuss recent studies that highlight their potential in cancer therapy and summarize clinical trials using these effector immune cells in adoptive cellular therapy for the treatment of cancer.

SUBMITTER: Sabry M

PROVIDER: S-EPMC7445022 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Killers at the crossroads: The use of innate immune cells in adoptive cellular therapy of cancer.

Sabry May M Lowdell Mark W MW

Stem cells translational medicine 20200516 9

Adoptive cell therapy (ACT) is an approach to cancer treatment that involves the use of antitumor immune cells to target residual disease in patients after completion of chemo/radiotherapy. ACT has several advantages compared with other approaches in cancer immunotherapy, including the ability to specifically expand effector cells in vitro before selection for adoptive transfer, as well as the opportunity for host manipulation in order to enhance the ability of transferred cells to recognize and ...[more]

PMID: 32416056

Similar Datasets

Project description:Abstract BACKGROUND Despite aggressive treatments, GBM continues to have unacceptably high mortality rates. Immune-checkpoint blockade and ACT have shown excellent results in other solid tumors, especially in melanoma. Unfortunately, these results have not been extrapolated to GBM. We have developed a novel platform for ACT using tumor mRNA-pulsed dendritic cells(DCs) to in-vitro expand polyclonal populations of tumor-reactive T-cells. This platform has shown promising effects in preclinical brain tumor models (Flores et al OncoImmunology 2015, Wildes et al CCR 2018, Flores et al NatureComm 2018) and being evaluated in clinical trials at UF Health (NCT02465268,NCT03334305). STUDY OBJECTIVE Evaluate whether immune-checkpoint blockade during ex-vivo expansion of antigen-specific T-cells impact their use in ACT. METHODS CMVpp65 was used as model antigen for in-vitro activation of T-cells. Mature pp65 mRNA-pulsed DCs from CMV+ healthy donors were co-cultured with T-cells in IL2-containing medium for 15days. We tested four checkpoint inhibitor groups: PD1(n= 6), PDL1(n= 4), TIM3(n= 7) and PD1+TIM3(n= 6) that were compared with non-blockade group, respectively. Checkpoint blockade was performed every 3days. T-cell proliferation, immune-phenotyping, and IFN-g release were analyzed. RESULTS Cell proliferation was lower in all the blockade groups but significantly lower in the TIM3 (p= 0.03) and TIM3+PD1 (p= 0.01) blockade groups. TIM3 expression was significantly lower in the TIM3 (p= 0.006) and PD1+TIM3 blockade groups (p= 0.0001). There was a trend of reduced pp65 tetramer positive in the TIM3 and PD1+TIM3 blockade groups (PD1+TIM3 subgroup at 3mcg/mL, p= 0.02) and lower INFg release in the TIM3 and PD1+TIM3 blockade groups. CONCLUSION The exact role of checkpoints during expansion of T-cells for ACT is not well understood. In our study checkpoint blockade with PD-1 or TIM-3 alone or in combination did not enhance T-cell expansion or function, in fact, appeared to have an inhibitory effect on measured parameters. Our results suggest that TIM-3 may have an activating role in our system.

Dataset Information

Killers at the crossroads: The use of innate immune cells in adoptive cellular therapy of cancer.

Publications

Killers at the crossroads: The use of innate immune cells in adoptive cellular therapy of cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets