Adoptive cell transfer (ACT) of autologous tumor‐infiltrating lymphocytes (TILs) to treat malignant melanoma: the dawn of a chimeric antigen receptor T (CAR‐T) cell therapy from autologous donor

145 Background: Clinical trials have shown that adoptive cell transfer therapy is a promising method for cancer treatment. In the current study, we aim to generate and characterize anti-tumor tumor-infiltrating lymphocytes from patients with breast cancer for adoptive cell transfer therapy. Methods: In vitro culture method was used to generate anti-tumor, tumor-infiltrating lymphocytes from patients with breast cancer. FACS analysis, ELISA, and Elispot assay were used to characterize tumor-infiltrating lymphocytes. Autologous anti-tumor tumor-infiltrating lymphocytes from patients with breast cancer were used in adoptive cell transfer therapy. Results: FACS analysis indicated that tumor-infiltrating lymphocytes were present in the tumor tissues, but not detectable in the normal breast tissues from patients with breast cancer. Tumor-infiltrating lymphocytes could be generated in vitro from fresh tumor specimens of patients with breast cancer. Both CD4 T cells and CD8 T cells were detected in tumor-infiltrating lymphocytes. Autologous tumor cells could also generate in vitro from fresh tumor tissue samples of patients with breast cancer. Among 22 samples screened, 6 samples (25%) of tumor-infiltrating lymphocytes are tumor-reactive. Anti-tumor, tumor-infiltrating lymphocytes could recognize autologous tumor cells and allogenic tumor cells. After a large scale T cell expansion, anti-tumor reactivity was maintained in tumor-infiltrating lymphocytes. All of tumor-infiltrating lymphocytes were NK cells in some samples from patients with breast cancer, and these NK cells could recognize autologous tumor cells and a panel of allogenic tumor cells. T cell cloning assay demonstrated that some of the tumor-reactive, tumor-infiltrating lymphocytes were CD4 T cells. Conclusions: The results suggest that anti-tumor, tumor-infiltrating lymphocytes may be generated from patients with breast cancer, which may be used in clinical applications of adoptive cell transfer therapy for patients with breast cancer. The clinical trial of adoptive cell transfer therapy using autologous anti-tumor tumor-infiltrating lymphocytes for patients with breast is under way.

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Immune cell labelling and tracking: implications for adoptive cell transfer therapies

EJNMMI Radiopharmacy and Chemistry ◽

10.1186/s41181-020-00116-7 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Filippo Galli ◽

Michela Varani ◽

Chiara Lauri ◽

Guido Gentiloni Silveri ◽

Livia Onofrio ◽

...

Keyword(s):

Cell Tracking ◽

Immune Cell ◽

Cell Types ◽

Adoptive Cell Transfer ◽

Cell Labelling ◽

Main Body ◽

Cell Transfer ◽

T Cell Therapy ◽

Car T Cell Therapy ◽

Car T

Abstract Background The understanding of the role of different immune cell subsets that infiltrate tumors can help researchers in developing new targeted immunotherapies to reactivate or reprogram them against cancer. In addition to conventional drugs, new cell-based therapies, like adoptive cell transfer, proved to be successful in humans. Indeed, after the approval of anti-CD19 CAR-T cell therapy, researchers are trying to extend this approach to other cancer or cell types. Main body This review focuses on the different approaches to non-invasively monitor the biodistribution, trafficking and fate of immune therapeutic cells, evaluating their efficacy at preclinical and clinical stages. PubMed and Scopus databases were searched for published articles on the imaging of cell tracking in humans and preclinical models. Conclusion Labelling specific immune cell subtypes with specific radiopharmaceuticals, contrast agents or optical probes can elucidate new biological mechanisms or predict therapeutic outcome of adoptive cell transfer therapies. To date, no technique is considered the gold standard to image immune cells in adoptive cell transfer therapies.

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Adoptive Cell Transfer of Autologous Tumor Infiltrating Lymphocytes and High-Dose Interleukin 2 in Select Solid Tumors

Case Medical Research ◽

10.31525/ct1-nct03991741 ◽

2019 ◽

Author(s):

Keyword(s):

Solid Tumors ◽

Interleukin 2 ◽

Tumor Infiltrating Lymphocytes ◽

Adoptive Cell Transfer ◽

High Dose ◽

Autologous Tumor ◽

Cell Transfer ◽

Infiltrating Lymphocytes

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Application of CAR-T Cell Therapy beyond Oncology: Autoimmune Diseases and Viral Infections

Biomedicines ◽

10.3390/biomedicines9010059 ◽

2021 ◽

Vol 9 (1) ◽

pp. 59

Author(s):

Ekaterina Zmievskaya ◽

Aygul Valiullina ◽

Irina Ganeeva ◽

Alexey Petukhov ◽

Albert Rizvanov ◽

...

Keyword(s):

T Cell ◽

Cell Therapy ◽

T Cell Activation ◽

Viral Infections ◽

Adoptive Cell Transfer ◽

Single Chain ◽

T Cell Therapy ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T

Adoptive cell transfer (ACT) has long been at the forefront of the battle with cancer that began last century with the therapeutic application of tumor-infiltrating lymphocytes (TILs) against melanoma. The development of novel ACT approaches led researchers and clinicians to highly efficient technologies based on genetically engineered T lymphocytes, with chimeric antigen receptor (CAR)-T cells as the most prominent example. CARs consist of an extracellular domain that represents the single-chain variable fragment (scFv) of a monoclonal antibody (mAb) responsible for target recognition and the intracellular domain, which was built from up to several signaling motifs that mediated T cell activation. The number of potential targets amenable for CAR-T cell therapy is expanding rapidly, which means that the tremendous success of this approach in oncology could be further translated to treating other diseases. In this review, we outlined modern trends and recent developments in CAR-T cell therapy from an unusual point of view by focusing on diseases beyond cancer, such as autoimmune disorders and viral infections, including SARS-CoV-2.

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