Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure

Wachsmann, Tassilo L. A.; Wouters, Anne K.; Remst, Dennis F. G.; Hagedoorn, Renate S.; Meeuwsen, Miranda H.; Diest, Eline van; Leusen, Jeanette H.W.; Kuball, Jürgen; Falkenburg, J.H. Frederik; Heemskerk, Mirjam H.M.

doi:10.1080/2162402x.2022.2033528

Cited by 27 publications

(22 citation statements)

References 37 publications

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“…Clinically, TCR-T-cells have been less extensively studied than CAR-T-cells. Whereas CAR-T-cells are redirected to surface antigens via an antibody-based targeting fraction, TCR-T-cells express a heterodimeric receptor that recognizes antigen-derived peptides presented in the HLA context [ 60 ]. TCR cell therapy was first used for the treatment of metastatic melanoma, in which lymphocytes engineered to express TCR capable of recognizing melanocyte differentiation antigen (MART-1) demonstrated beneficial effects in the treatment of the disease [ 61 ].…”

Section: Immunotherapeutic Approach To Control Primary Brain Cancersmentioning

confidence: 99%

Recent Emerging Immunological Treatments for Primary Brain Tumors: Focus on Chemokine-Targeting Immunotherapies

Ardizzone

Basilotta

Filippone

et al. 2023

Cells

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Primary brain tumors are a leading cause of death worldwide and are characterized by extraordinary heterogeneity and high invasiveness. Current drug and radiotherapy therapies combined with surgical approaches tend to increase the five-year survival of affected patients, however, the overall mortality rate remains high, thus constituting a clinical challenge for which the discovery of new therapeutic strategies is needed. In this field, novel immunotherapy approaches, aimed at overcoming the complex immunosuppressive microenvironment, could represent a new method of treatment for central nervous system (CNS) tumors. Chemokines especially are a well-defined group of proteins that were so named due to their chemotactic properties of binding their receptors. Chemokines regulate the recruitment and/or tissue retention of immune cells as well as the mobilization of tumor cells that have undergone epithelial–mesenchymal transition, promoting tumor growth. On this basis, this review focuses on the function and involvement of chemokines and their receptors in primary brain tumors, specifically examining chemokine-targeting immunotherapies as one of the most promising strategies in neuro-oncology.

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Section: Immunotherapeutic Approach To Control Primary Brain Cancersmentioning

confidence: 99%

Recent Emerging Immunological Treatments for Primary Brain Tumors: Focus on Chemokine-Targeting Immunotherapies

Ardizzone

Basilotta

Filippone

et al. 2023

Cells

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“…When sparse intracellular antigens become the target, the use of artificial TCR-T lymphocytes is more preferable and has a number of advantages that result from the high specificity and sensitivity of natural TCRs [ 119 ]. At the same time, the use of artificial TCRs with high affinity for the target antigen, similar to CAR-T, can lead to a decrease in recognition efficiency, nonspecific activation, and early depletion of T cells [ 120 , 121 ].…”

Section: Practical Valuementioning

confidence: 99%

The Enigmatic Nature of the TCR-pMHC Interaction: Implications for CAR-T and TCR-T Engineering

Shevyrev

Tereshchenko

Sennikov

2022

IJMS

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The interaction of the T-cell receptor (TCR) with a peptide in the major histocompatibility complex (pMHC) plays a central role in the adaptive immunity of higher chordates. Due to the high specificity and sensitivity of this process, the immune system quickly recognizes and efficiently responds to the appearance of foreign and altered self-antigens. This is important for ensuring anti-infectious and antitumor immunity, in addition to maintaining self-tolerance. The most common parameter used for assessing the specificity of TCR-pMHC interaction is affinity. This thermodynamic characteristic is widely used not only in various theoretical aspects, but also in practice, for example, in the engineering of various T-cell products with a chimeric (CAR-T) or artificial (TCR-engineered T-cell) antigen receptor. However, increasing data reveal the fact that, in addition to the thermodynamic component, the specificity of antigen recognition is based on the kinetics and mechanics of the process, having even greater influence on the selectivity of the process and T lymphocyte activation than affinity. Therefore, the kinetic and mechanical aspects of antigen recognition should be taken into account when designing artificial antigen receptors, especially those that recognize antigens in the MHC complex. This review describes the current understanding of the nature of the TCR-pMHC interaction, in addition to the thermodynamic, kinetic, and mechanical principles underlying the specificity and high sensitivity of this interaction.

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“…However, an increase in the antigen exposure significantly disrupts the expansion of CAR-T cells, a phenotype characterized by the increased expression of coinhibitory molecules. On the contrary, TCR-T cells proved to be better at high antigenic pressure, maintaining stable expansion rates with a lower expression of coinhibitory molecules and a comparable clearance of tumor cells [ 107 ]. Research is still ongoing, but up until this moment, there is still no approved TCR-T-cell therapy for HER2-positive tumors.…”

Section: Her2 As a Target For Therapymentioning

confidence: 99%

The Role of Tumor-Associated Antigen HER2/neu in Tumor Development and the Different Approaches for Using It in Treatment: Many Choices and Future Directions

Alrhmoun

Сенников

2022

Cancers

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The treatment of HER2-positive cancers has changed significantly over the past ten years thanks to a significant number of promising new approaches that have been added to our arsenal in the fight against cancer, including monoclonal antibodies, inhibitors of tyrosine kinase, antibody–drug conjugates, vaccination, and particularly, adoptive-T-cell therapy after its great success in hematological malignancies. Equally important is the new methodology for determining patients eligible for targeted HER2 therapy, which has doubled the number of patients who can benefit from these treatments. However, despite the initial enthusiasm, there are still several problems in this field represented by drug resistance and tumor recurrence that require the further development of new more efficient drugs. In this review, we discuss various approaches for targeting the HER2 molecule in cancer treatment, highlighting their benefits and drawbacks, along with the different mechanisms responsible for resistance to HER2-targeted therapies and how to overcome them.

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Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure

Cited by 27 publications

References 37 publications

Recent Emerging Immunological Treatments for Primary Brain Tumors: Focus on Chemokine-Targeting Immunotherapies

Recent Emerging Immunological Treatments for Primary Brain Tumors: Focus on Chemokine-Targeting Immunotherapies

The Enigmatic Nature of the TCR-pMHC Interaction: Implications for CAR-T and TCR-T Engineering

The Role of Tumor-Associated Antigen HER2/neu in Tumor Development and the Different Approaches for Using It in Treatment: Many Choices and Future Directions

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