Adoptive Immunotherapy Based on Chain-Centric TCRs in Treatment of Infectious Diseases

Kalinina, Anastasiia; Nesterenko, L. N.; Bruter, Alexandra V.; Balunets, D. V.; Chudakov, Dmitriy M.; Izraelson, Mark; Britanova, Olga V.; Хромых, Л. М.; Kazansky, Dmitry

doi:10.1016/j.isci.2020.101854

Cited by 12 publications

(21 citation statements)

References 49 publications

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“…cDNA libraries were prepared and raw data was processed as described previously ( Egorov et al., 2015 ; Bolotin et al., 2015 ; Shugay et al., 2014 ). For detailed description of cDNA libraries analysis and selection of dominant-active TCRα-SM refer to ( Kalinina et al., 2020 ).…”

Section: Before You Beginmentioning

confidence: 99%

“… Timing: 17–20 days (4 days for cloning TCRa-SM into the pTZ vector; 7–10 days for sequencing and analyses, depending on a facility; 4 days for cloning TCRa-SM into the MigR1 -PGK vector) Note: As the template for amplification of V-, J-, and C-segment of TCRa, use cDNA (20 ng) of salmonella-specific memory cells of a B10.D2(R101) mouse that were enriched in vitro by re-stimulation with salmonella. For detailed methods of in vivo generation and in vitro enrichment of salmonella-specific memory T cells refer to ( Kalinina et al., 2020 ). Using primers AgeI_forward and Unique_reverse (10 μM each), amplify V-segment (Fragment 1).…”

Section: Before You Beginmentioning

confidence: 99%

“…Note: As the template for amplification of V-, J-, and C-segment of TCRa, use cDNA (20 ng) of salmonella-specific memory cells of a B10.D2(R101) mouse that were enriched in vitro by re-stimulation with salmonella. For detailed methods of in vivo generation and in vitro enrichment of salmonella-specific memory T cells refer to ( Kalinina et al., 2020 ).…”

Section: Before You Beginmentioning

confidence: 99%

“…This protocol describes how to generate salmonella-specific TCRα-modified mouse T cells by retroviral transduction and evaluate their functional activity in vivo in the mouse model of salmonellosis. For complete details on the use and execution of this protocol, please refer to Kalinina et al. (2020) .…”

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Kalinina et al. (2020) .…”

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confidence: 99%

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Generation of TCRα-transduced T cells for adoptive transfer therapy of salmonellosis in mice

et al. 2021

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Summary Adoptive transfer therapy has great potential to treat diseases such as cancer as well as autoimmune and infectious diseases. Identification of chain-centric T cell receptors (TCRs) with the dominant-active antigen-specific α-chains (TCRα) can significantly improve the efficacy of adoptive cell therapy while reducing time, labor, and costs of generation of TCR-modified antigen-specific T cells. This protocol describes how to generate salmonella-specific TCRα-modified mouse T cells by retroviral transduction and evaluate their functional activity in vivo in the mouse model of salmonellosis. For complete details on the use and execution of this protocol, please refer to Kalinina et al. (2020) .

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Section: Before You Beginmentioning

confidence: 99%

Section: Before You Beginmentioning

confidence: 99%

Section: Before You Beginmentioning

confidence: 99%

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Kalinina et al. (2020) .…”

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confidence: 99%

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Generation of TCRα-transduced T cells for adoptive transfer therapy of salmonellosis in mice

et al. 2021

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Analysis of thymic generation of shared T‐cell receptor α repertoire associated with recognition of tumor antigens shows no preference for neoantigens over wild‐type antigens

et al. 2023

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Background The number of mutations in cancer cells is an important predictor of a positive response to cancer immunotherapy. It has been suggested that the neoantigens produced by these mutations are more immunogenic than nonmutated tumor antigens, which are likely to be protected by immunological tolerance. However, the mechanisms of tolerance as regards tumor antigens are incompletely understood. Methods Here, we have analyzed the impact of thymic negative selection on shared T‐cell receptor (TCR) repertoire associated with the recognition of either mutated or nonmutated tumor antigens by comparing previously known TCR—antigen—pairs to TCR repertoires of 21 immunologically healthy individuals. Results Our results show that TCRα chains associated with either type of tumor antigens are readily generated in the thymus, at a frequency similar to TCRα chains associated with nonself. In the peripheral repertoire, the relative clone size of nonself‐associated chains is higher than that of the tumor antigens, but importantly, there is no difference between TCRα chains associated with mutated or nonmutated tumor antigens. Conclusion This suggests that the tolerance mechanisms protecting nonmutated tumor antigens are non‐deletional and therefore potentially reversible. As unmutated antigens are, unlike mutations, shared by a large number of patients, they may offer advantages in designing immunological approaches to cancer treatment.

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Profiling T cell receptor β‐chain in responders after immunization with recombinant hepatitis B vaccine

Dong¹,

Yang

et al. 2021

The Journal of Gene Medicine

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Background: T cells with edited T cell receptor β-chain variable (TRBV) are involved in the immune response to recombinant hepatitis B surface antigen (rHBsAg) vaccine and the production of hepatitis B surface antibody (HBsAb). The immune repertoire (IR) profile and mechanism of vaccination positive responders (VPR) with rHBsAg are not fully understood.Methods: The IR of six VPRs (HBsAb+, HbsAg-) with rHBsAg vaccination was established by the high throughput sequencing technique and bioinformatics analysis and compared with those in five vaccination negative responders (VNRs) (HbsAb-, HbsAg-) who were also inoculated with rHBsAg. The repertoire features of the BV, BJ and V (CDR3) J genes and immune diversity in peripheral blood mononuclear cells, respectively, were analyzed for each subject.Results: There was no significant difference in sequencing amplification indices of each sample. However, TRBV15/BJ2-3 demonstrated significantly high expression levels in VPR compared to those in the VNR group (both p < 0.05). Further results showed that the BV15/BJ2-5 level was significantly increased for VPR compared to that of VNR group. Interestingly, the motif of CDR3 in TRBV15/BJ2-5 was mostly expressed as "GGETQ" or "GETQ". Additionally, there was no remarkable difference between the two groups of distribution with respect to the different clone expression levels of V (CDR3) J. Conclusions:The features of IR in the VPR and VNR will contribute to the exploration of the mechanism of the positive response to rHBsAg, and also contribute to development of optimized hepatitis B vaccine, in addition to providing a partial interpretation of the VNR who has a relatively low infection with HBV.

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Adoptive Immunotherapy Based on Chain-Centric TCRs in Treatment of Infectious Diseases

Cited by 12 publications

References 49 publications

Generation of TCRα-transduced T cells for adoptive transfer therapy of salmonellosis in mice

Generation of TCRα-transduced T cells for adoptive transfer therapy of salmonellosis in mice

Analysis of thymic generation of shared T‐cell receptor α repertoire associated with recognition of tumor antigens shows no preference for neoantigens over wild‐type antigens

Profiling T cell receptor β‐chain in responders after immunization with recombinant hepatitis B vaccine

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