Cancer immunotherapy: current opportunities and perspectives

Cancer immunotherapy is a relatively new and promising method of treating neoplasms. Understanding the antigen-directed cytotoxicity of T-lymphocytes has become one of the central directions in involving the immune system in the fight against cancer. Basic research in this area has led to the invention of checkpoint inhibitors, adoptive T-cell therapy, and cancer vaccines. Cytokines can enhance the action of T-lymphocytes for their ability to directly stimulate effector and stromal cells in tumor focus and enhance recognition of tumor cells by cytotoxic effector cells. They were the first in cancer immunotherapy and remain relevant to this day. Today, immunotherapy is an effective treatment for most malignant tumors, including melanoma, non-small cell lung cancer, liver, stomach, bladder, cervical cancer, some types of breast cancer, lymphoma, etc. However, immunotherapy of some malignant tumors is ineffective, therefore, the development of new and improvement of existing immunotherapy agents is actively underway, and there is a hope that the indications for its use will expand. For this purpose, this review discusses the principles of action of various classes of immunotherapeutic anticancer agents, namely cytokines, immune checkpoint inhibitors, and adaptive T-cell therapy. The work highlights their indications, efficacy and toxicity from the use of each class of drugs, as well as the prospects for the development of immunotherapeutic anticancer drugs.

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Simultaneous induction of Tri-antigen specific cytotoxic T lymphocytes(CTLs) using DCs transferred with WT1, survivin and TERT mRNA for adoptive T cell therapy

Cytotherapy ◽

10.1016/j.jcyt.2014.01.061 ◽

2014 ◽

Vol 16 (4) ◽

pp. S20

Author(s):

H. Sohn ◽

H. Lee ◽

H. Kim ◽

H. Cho ◽

H. Park ◽

...

Keyword(s):

T Cell ◽

T Lymphocytes ◽

Cell Therapy ◽

Cytotoxic T Lymphocytes ◽

Adoptive T Cell Therapy ◽

T Cell Therapy ◽

Simultaneous Induction

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Myeloid-Derived Suppressor Cells: Implications in the Resistance of Malignant Tumors to T Cell-Based Immunotherapy

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.707198 ◽

2021 ◽

Vol 9 ◽

Author(s):

Houhui Shi ◽

Kai Li ◽

Yanghong Ni ◽

Xiao Liang ◽

Xia Zhao

Keyword(s):

T Cell ◽

Cancer Patients ◽

Oncolytic Virus ◽

Malignant Tumors ◽

Checkpoint Inhibitors ◽

Suppressor Cells ◽

Immunological Response ◽

Adoptive T Cell Therapy ◽

Myeloid Derived Suppressor Cells ◽

T Cell Therapy

T lymphocytes function as major players in antigen-mediated cytotoxicity and have become powerful tools for exploiting the immune system in tumor elimination. Several types of T cell-based immunotherapies have been prescribed to cancer patients with durable immunological response. Such strategies include immune checkpoint inhibitors, adoptive T cell therapy, cancer vaccines, oncolytic virus, and modulatory cytokines. However, the majority of cancer patients still failed to take the advantage of these kinds of treatments. Currently, extensive attempts are being made to uncover the potential mechanism of immunotherapy resistance, and myeloid-derived suppressor cells (MDSCs) have been identified as one of vital interpretable factors. Here, we discuss the immunosuppressive mechanism of MDSCs and their contributions to failures of T cell-based immunotherapy. Additionally, we summarize combination therapies to ameliorate the efficacy of T cell-based immunotherapy.

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Adoptive T-Cell Therapy: Optimizing Chemokine Receptor-Mediated Homing of T Cells in Cancer Immunotherapy

Cancer Immunology ◽

10.1007/978-3-662-44946-2_14 ◽

2014 ◽

pp. 263-282

Author(s):

Imran Siddiqui ◽

Alberto Mantovani ◽

Paola Allavena

Keyword(s):

T Cells ◽

T Cell ◽

Cell Therapy ◽

Cancer Immunotherapy ◽

Chemokine Receptor ◽

Adoptive T Cell Therapy ◽

T Cell Therapy

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CRISPR/Cas9 revitalizes adoptive T-cell therapy for cancer immunotherapy

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02076-5 ◽

2021 ◽

Vol 40 (1) ◽

Cited By ~ 1

Author(s):

Sasan Ghaffari ◽

Nastaran Khalili ◽

Nima Rezaei

Keyword(s):

T Cells ◽

T Cell ◽

Cell Therapy ◽

Cancer Immunotherapy ◽

Cell Receptor ◽

Adoptive T Cell Therapy ◽

Therapeutic Modality ◽

T Cell Therapy ◽

Car T Cells ◽

Car T

AbstractCancer immunotherapy has gained attention as the supreme therapeutic modality for the treatment of various malignancies. Adoptive T-cell therapy (ACT) is one of the most distinctive modalities of this therapeutic approach, which seeks to harness the potential of combating cancer cells by using autologous or allogenic tumor-specific T-cells. However, a plethora of circumstances must be optimized to produce functional, durable, and efficient T-cells. Recently, the potential of ACT has been further realized by the introduction of novel gene-editing platforms such as the CRISPR/Cas9 system; this technique has been utilized to create T-cells furnished with recombinant T-cell receptor (TCR) or chimeric antigen receptor (CAR) that have precise tumor antigen recognition, minimal side effects and treatment-related toxicities, robust proliferation and cytotoxicity, and nominal exhaustion. Here, we aim to review and categorize the recent breakthroughs of genetically modified TCR/CAR T-cells through CRISPR/Cas9 technology and address the pearls and pitfalls of each method. In addition, we investigate the latest ongoing clinical trials that are applying CRISPR-associated TCR/CAR T-cells for the treatment of cancers.

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4-1BB (CD137) in anticancer chimeras

Journal of Experimental Medicine ◽

10.1084/jem.20201562 ◽

2020 ◽

Vol 217 (12) ◽

Author(s):

Ignacio Melero ◽

Pedro Berraondo

Keyword(s):

T Cell ◽

T Lymphocytes ◽

Cell Therapy ◽

Cytotoxic T Lymphocytes ◽

Adoptive T Cell Therapy ◽

T Cell Therapy ◽

Costimulatory Signals

4-1BB (CD137, TNFRSF9) mediates costimulatory signals important for activation and persistence of cytotoxic T lymphocytes. In this issue of JEM, Oda et al. (https://doi.org/10.1084/jem.20191166) report on a chimeric construction encompassing extracellular Fas and intracellular 4-1BB to dramatically improve adoptive T cell therapy.

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ID:4007 Immune-cell base for cancer therapy

Biomedical Research and Therapy ◽

10.15419/bmrat.v4is.217 ◽

2017 ◽

Vol 4 (S) ◽

pp. 10

Author(s):

Van Thanh Ta ◽

Thinh Huy Tran ◽

Binh Thanh Nguyen ◽

Linh Quy Nguyen ◽

Hoai Quy Nguyen ◽

...

Keyword(s):

T Cell ◽

T Lymphocytes ◽

Cell Therapy ◽

Immune Cell ◽

Specific Antigen ◽

Cell Receptor ◽

Adoptive T Cell Therapy ◽

Target Cells ◽

T Cell Therapy ◽

Mhc Molecules

The development of immune cell-based approaches for treatment of cancer has been actively investigated for many years. One strategy that has been demonstrated as an effective method for cancer treatment is adoptive T cell therapy. The principle of this method is using Cytotoxic T lymphocytes (CTL), a crucial component of the adaptive immune system that aids in the control of intracellular pathogens. Effector CTL have the capacity to promote the apoptotic death of specifically targeted cells, using a combination of granule (perforin/granzyme)-and receptor (Fas/tumor necrosis factor)-mediated mechanisms. CTL recognize specific antigen on target cells using an unique T-cell receptor (TCR) when they are presented by class I major histocompatibility (MHC) molecules. In this study, we demonstrated that T lymphocytes were activated and dramatically expanded by stimulation with anti-CD3/CD28 antibodies and culture in the present of IL-2, IL-15 and IL-21 cytokines. These T cells exhibited a predominantly activated phenotype as manifested by an increase in the percentage of cells expressing CD8 and generation of various cytokines such as IL-2, INFγ and TNFa. These findings indicate that stimulation by anti- CD3/CD28 generated effector CTL in adoptive T-cell therapy for cancer.

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Future role for adoptive T-cell therapy in checkpoint inhibitor-resistant metastatic melanoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-000668 ◽

2020 ◽

Vol 8 (2) ◽

pp. e000668

Author(s):

Troels Holz Borch ◽

Rikke Andersen ◽

Eva Ellebaek ◽

Özcan Met ◽

Marco Donia ◽

...

Keyword(s):

T Cell ◽

Cell Therapy ◽

Metastatic Melanoma ◽

Tumor Antigens ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Adoptive T Cell Therapy ◽

Great Promise ◽

T Cell Therapy ◽

Link Type

Personalized cell therapy targeting tumor antigens with expanded tumor-infiltrating lymphocytes (TILs) has shown great promise in metastatic melanoma (MM) since the 90s. However, MM was first-in line to benefit from the wave of checkpoint inhibitors (CPI), which shifted the focus of immunotherapy almost fully to immune CPI. Still, the majority of patients fail to benefit from CPI treatment, raising the intriguing question on how TIL therapy may fit into the changing landscape of melanoma treatment. We took advantage of data from a unique cohort of patients with MM treated with T-cell therapy in consecutive clinical trials at our institution across the last 10 years. Based on detailed data on patient characteristics, pre-TIL and post-TIL treatments and long-term follow-up, we were able to address the important issue of how TIL therapy can be positioned in the current CPI era. We found that previous progression on anticytotoxic T-lymphocyte-associated protein 4 do not seem to harm neither rate nor duration of response to TIL therapy. Importantly, even in the hard-to-treat population of patients who progressed on antiprogrammed cell death protein 1 (anti-PD-1), an objective response rate of 32% was achieved, including durable responses. Yet, median progression-free survival was reduced in this anti-PD-1 refractory population. Trial registration number: ClinicalTrials.gov ID: NCT00937625, NCT02379195 and NCT02354690.

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Therapeutic Applications of Engineered Chimeric Antigen Receptors-T cell for Cancer Therapy

10.20944/preprints202110.0368.v1 ◽

2021 ◽

Author(s):

Amina Hussain

Keyword(s):

T Cells ◽

T Cell ◽

T Lymphocytes ◽

Cell Therapy ◽

Malignant Tumors ◽

Adoptive Cell Therapy ◽

Clinical Results ◽

Antigen Receptors ◽

Chimeric Antigen Receptors ◽

T Cell Therapy

Findings of new targeted treatments with adequate safety evaluations is essential for better cancer cures and mortality rates. Immunotherapy holds promise for patients with relapsed disease, with the ability to elicit long-term remissions. Emerging promising clinical results in B-cell malignancy using gene-altered T-lymphocytes uttering chimeric antigen receptors have sparked a lot of interest. This treatment could open the path for a major difference in the way we treat tumors that are resistant or recurring. Genetically altered T cells used to produce tumor-specific chimeric antigen receptors are resurrected field of adoptive cell therapy by demonstrating remarkable success in the treatment of malignant tumors. Because of the molecular complexity of chimeric antigen receptors -T cells, a variety of engineering approaches to improve safety and effectiveness are necessary to realize larger therapeutic uses. In this study, we investigate at new strategies for enhancing chimeric antigen receptors-T cell therapy by altering chimeric antigen receptors proteins, T lymphocytes, and their relations with other solid tumor microenvironment (TME) aspects.

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