Top

Journal of Experimental & Clinical Cancer Research

Published in:

Open Access 01-12-2024 | Cancer Therapy | Review

GMP-manufactured CRISPR/Cas9 technology as an advantageous tool to support cancer immunotherapy

Authors: M Caforio, S Iacovelli, C Quintarelli, F Locatelli, Valentina Folgiero

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2024

Abstract

Background

CRISPR/Cas9 system to treat human-related diseases has achieved significant results and, even if its potential application in cancer research is improving, the application of this approach in clinical practice is still a nascent technology.

Main body

CRISPR/Cas9 technology is not yet used as a single therapy to treat tumors but it can be combined with traditional treatment strategies to provide personalized gene therapy for patients. The combination with chemotherapy, radiation and immunotherapy has been proven to be a powerful means of screening, identifying, validating and correcting tumor targets. Recently, CRISPR/Cas9 technology and CAR T-cell therapies have been integrated to open novel opportunities for the production of more efficient CAR T-cells for all patients. GMP-compatible equipment and reagents are already available for several clinical-grade systems at present, creating the basis and framework for the accelerated development of novel treatment methods.

Conclusion

Here we will provide a comprehensive collection of the actual GMP-grade CRISPR/Cas9-mediated approaches used to support cancer therapy highlighting how this technology is opening new opportunities for treating tumors.

European commision. EudraLex - Volume 4 - Good Manufacturing Practice (GMP) guidelines. 2003. https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en.

European medicine agency. Good manufacturing practice. https://www.ema.europa.eu/en/human-regulatory-overview/research-and-development/compliance-research-and-development/good-manufacturing-practice.

Palmer DC, Webber BR, Patel Y, Johnson MJ, Kariya CM, Lahr WS, et al. Internal checkpoint regulates T cell neoantigen reactivity and susceptibility to PD1 blockade. Med. 2022. https://doi.org/10.1016/j.medj.2022.07.008.CrossRefPubMed

Shy BR, Vykunta VS, Ha A, Talbot A, Roth TL, Nguyen DN, et al. High-yield genome engineering in primary cells using a hybrid ssDNA repair template and small-molecule cocktails. Nat Biotechnol. 2023. https://doi.org/10.1038/s41587-022-01418-8.CrossRefPubMed

Basar R, Daher M, Uprety N, Gokdemir E, Alsuliman A, Ensley E, et al. Large-scale GMP-compliant CRISPR-Cas9-mediated deletion of the glucocorticoid receptor in multivirus-specific T cells. Blood Adv. 2020. https://doi.org/10.1182/bloodadvances.2020001977.CrossRefPubMedPubMedCentral

Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol. 1987. https://doi.org/10.1128/jb.169.12.5429-5433.1987.CrossRefPubMedPubMedCentral

Wiedenheft B, Sternberg SH, Doudna JA. RNA-guided genetic silencing systems in bacteria and archaea. Nature. 2012. https://doi.org/10.1038/nature10886.CrossRefPubMed

Makarova KS, Wolf YI, Iranzo J, Shmakov SA, Alkhnbashi OS, Brouns SJJ, et al. Evolutionary classification of CRISPR-Cas systems: a burst of class 2 and derived variants. Nat Rev Microbiol. 2020. https://doi.org/10.1038/s41579-019-0299-x.CrossRefPubMed

Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, et al. RNA-guided Hum Genome Eng via Cas9 Sci. 2013. https://doi.org/10.1126/science.1232033.CrossRef

10.

Sapranauskas R, Gasiunas G, Fremaux C, Barrangou R, Horvath P, Siksnys V. The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli. Nucleic Acids Res. 2011. https://doi.org/10.1093/nar/gkr606.CrossRefPubMedPubMedCentral

11.

Horvath P, Barrangou R. CRISPR/Cas, the immune system of bacteria and archaea. Science. 2010. https://doi.org/10.1126/science.1179555.CrossRefPubMed

12.

Jiang F, Doudna JA. CRISPR-Cas9 structures and mechanisms. Annu Rev Biophys. 2017. https://doi.org/10.1146/annurev-biophys-062215-010822.CrossRefPubMed

13.

Sander JD, Joung JK. CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol. 2014. https://doi.org/10.1038/nbt.2842.CrossRefPubMedPubMedCentral

14.

Heyer W, Ehmsen KT, Liu J. Regulation of homologous recombination in eukaryotes. Annu Rev Genet. 2010. https://doi.org/10.1146/annurev-genet-051710-150955.CrossRefPubMedPubMedCentral

15.

Gaj T, Gersbach CA. Barbas CF3. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013. https://doi.org/10.1016/j.tibtech.2013.04.004.CrossRefPubMedPubMedCentral

16.

Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD. Genome editing with engineered zinc finger nucleases. Nat Rev Genet. 2010. https://doi.org/10.1038/nrg2842.CrossRefPubMed

17.

Cyranoski D. CRISPR gene-editing tested in a person for the first time. Nature. 2016. https://doi.org/10.1038/nature.2016.20988.CrossRefPubMed

18.

Lu Y, Xue J, Deng T, Zhou X, Yu K, Deng L, et al. Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer. Nat Med. 2020. https://doi.org/10.1038/s41591-020-0840-5.CrossRefPubMedPubMedCentral

19.

Rupp LJ, Schumann K, Roybal KT, Gate RE, Ye CJ, Lim WA, et al. CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells. Sci Rep. 2017. https://doi.org/10.1038/s41598-017-00462-8.CrossRefPubMedPubMedCentral

20.

Benjamin R, Graham C, Yallop D, Jozwik A, Mirci-Danicar OC, Lucchini G, et al. Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies. Lancet. 2020. https://doi.org/10.1016/S0140-6736(20)32334-5.CrossRefPubMedPubMedCentral

21.

Balke-Want H, Keerthi V, Gkitsas N, Mancini AG, Kurgan GL, Fowler C, et al. Homology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing. Mol Cancer. 2023. https://doi.org/10.1186/s12943-023-01799-7.CrossRefPubMedPubMedCentral

22.

Yang Y. Cancer immunotherapy: harnessing the immune system to battle cancer. J Clin Invest. 2015. https://doi.org/10.1172/JCI83871.CrossRefPubMedPubMedCentral

23.

Turtle CJ, Hanafi L, Berger C, Gooley TA, Cherian S, Hudecek M, et al. CD19 CAR-T cells of defined CD4+:CD8 + composition in adult B cell ALL patients. J Clin Invest. 2016. https://doi.org/10.1172/JCI85309.CrossRefPubMedPubMedCentral

24.

Liu Y, Hu Y, Xue J, Li J, Yi J, Bu J, et al. Advances in immunotherapy for triple-negative breast cancer. Mol Cancer. 2023. https://doi.org/10.1186/s12943-023-01850-7.CrossRefPubMedPubMedCentral

25.

Balkwill F, CharlKellie A, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell. 2005. https://doi.org/10.1016/j.ccr.2005.02.013.CrossRefPubMed

26.

Kerkar SP, Restifo NP. Cellular constituents of immune escape within the tumor microenvironment. Cancer Res. 2012. https://doi.org/10.1158/0008-5472.CAN-11-4094.CrossRefPubMedPubMedCentral

27.

Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer. 2005. https://doi.org/10.1038/nrc1586.CrossRefPubMed

28.

Aguilar EJ, Ricciuti B, Gainor JF, Kehl KL, Kravets S, Dahlberg S, et al. Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Ann Oncol. 2019. https://doi.org/10.1093/annonc/mdz288.CrossRefPubMed

29.

Chism DD. Urothelial Carcinoma of the bladder and the rise of Immunotherapy. J Natl Compr Canc Netw. 2017. https://doi.org/10.6004/jnccn.2017.7036.CrossRefPubMed

30.

Stege H, Haist M, Nikfarjam U, Schultheis M, Heinz J, Pemler S, et al. The Status of Adjuvant and Neoadjuvant Melanoma Therapy, New Developments and Upcoming challenges. Target Oncol. 2021. https://doi.org/10.1007/s11523-021-00840-3.CrossRefPubMedPubMedCentral

31.

Naidoo J, Wang X, Woo KM, Iyriboz T, Halpenny D, Cunningham J, et al. Pneumonitis in patients treated with Anti-programmed Death-1/Programmed death Ligand 1 therapy. J Clin Oncol. 2017. https://doi.org/10.1200/JCO.2016.68.2005.CrossRefPubMed

32.

Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events Associated with Immune Checkpoint Blockade. N Engl J Med. 2018. https://doi.org/10.1056/NEJMra1703481.CrossRefPubMedPubMedCentral

33.

Xu Y, Chen C, Guo Y, Hu S, Sun Z. Effect of CRISPR/Cas9-Edited PD-1/PD-L1 on Tumor Immunity and Immunotherapy. Front Immunol. 2022. https://doi.org/10.3389/fimmu.2022.848327.CrossRefPubMedPubMedCentral

34.

Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 2013. https://doi.org/10.1038/nprot.2013.143.CrossRefPubMedPubMedCentral

35.

Schumann K, Lin S, Boyer E, Simeonov DR, Subramaniam M, Gate RE, et al. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins. Proc Natl Acad Sci U S A. 2015. https://doi.org/10.1073/pnas.1512503112.CrossRefPubMedPubMedCentral

36.

Su S, Hu B, Shao J, Shen B, Du J, Du Y, et al. CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients. Sci Rep. 2016. https://doi.org/10.1038/srep20070.CrossRefPubMedPubMedCentral

37.

Zhang C, Peng Y, Hublitz P, Zhang H, Dong T. Genetic abrogation of immune checkpoints in antigen-specific cytotoxic T-lymphocyte as a potential alternative to blockade immunotherapy. Sci Rep. 2018. https://doi.org/10.1038/s41598-018-23803-7.CrossRefPubMedPubMedCentral

38.

Su S, Zou Z, Chen F, Ding N, Du J, Shao J, et al. CRISPR-Cas9-mediated disruption of PD-1 on human T cells for adoptive cellular therapies of EBV positive gastric cancer. Oncoimmunology. 2016. https://doi.org/10.1080/2162402X.2016.1249558.CrossRefPubMedPubMedCentral

39.

Zhao Z, Shi L, Zhang W, Han J, Zhang S, Fu Z, et al. CRISPR knock out of programmed cell death protein 1 enhances anti-tumor activity of cytotoxic T lymphocytes. Oncotarget. 2017. https://doi.org/10.18632/oncotarget.23730.CrossRefPubMedPubMedCentral

40.

Tian X, Gu T, Patel S, Bode AM, Lee M, Dong Z. CRISPR/Cas9 - an evolving biological tool kit for cancer biology and oncology. NPJ Precis Oncol. 2019. https://doi.org/10.1038/s41698-019-0080-7.CrossRefPubMedPubMedCentral

41.

Tsui CK, Barfield RM, Fischer CR, Morgens DW, Li A, Smith BAH, et al. CRISPR-Cas9 screens identify regulators of antibody-drug conjugate toxicity. Nat Chem Biol. 2019. https://doi.org/10.1038/s41589-019-0342-2.CrossRefPubMedPubMedCentral

42.

Ministro JH, Oliveira SS, Oliveira JG, Cardoso M, Aires-da-Silva F, Corte-Real S, et al. Synthetic antibody discovery against native antigens by CRISPR/Cas9-library generation and endoplasmic reticulum screening. Appl Microbiol Biotechnol. 2020. https://doi.org/10.1007/s00253-020-10423-3.CrossRefPubMed

43.

Wei J, Marisetty A, Schrand B, Gabrusiewicz K, Hashimoto Y, Ott M, et al. Osteopontin mediates glioblastoma-associated macrophage infiltration and is a potential therapeutic target. J Clin Invest. 2019. https://doi.org/10.1172/JCI121266.CrossRefPubMedPubMedCentral

44.

Yang J, Li Z, Shen M, Wang Y, Wang L, Li J, et al. Programmable Unlocking Nano-Matryoshka-CRISPR precisely reverses immunosuppression to Unleash Cascade amplified adaptive Immune response. Adv Sci (Weinh). 2021. https://doi.org/10.1002/advs.202100292.CrossRefPubMedPubMedCentral

45.

Ferreira LMR, Muller YD, Bluestone JA, Tang Q. Next-generation regulatory T cell therapy. Nat Rev Drug Discov. 2019. https://doi.org/10.1038/s41573-019-0041-4.CrossRefPubMedPubMedCentral

46.

Zhou J, Liu M, Sun H, Feng Y, Xu L, Chan AWH, et al. Hepatoma-intrinsic CCRK inhibition diminishes myeloid-derived suppressor cell immunosuppression and enhances immune-checkpoint blockade efficacy. Gut. 2018. https://doi.org/10.1136/gutjnl-2017-314032.CrossRefPubMed

47.

Kelton W, Waindok AC, Pesch T, Pogson M, Ford K, Parola C, et al. Reprogramming MHC specificity by CRISPR-Cas9-assisted cassette exchange. Sci Rep. 2017. https://doi.org/10.1038/srep45775.CrossRefPubMedPubMedCentral

48.

Liu B, Yan J, Su S, Shao J, Zhao Y, Xu Q, Yang Y, Zou Z, Huang X. J. Wei. A phase I/II trial of CRISPR-Cas9-mediated PD-1 knockout Epstein-Barr Virus cytotoxic lymphocytes (EBV-CTLs) for advanced stage EBV associated malignancies. 2018;29:64 – 5.

49.

Thara E, Dorff TB, Pinski JK, Quinn DI. Vaccine therapy with sipuleucel-T (Provenge) for prostate cancer. Maturitas. 2011. https://doi.org/10.1016/j.maturitas.2011.04.012.CrossRefPubMed

50.

Naser W, Maymand S, Dlugolenski D, Basheer F, Ward AC. The role of cytokine-inducible SH2 domain-containing protein (CISH) in the regulation of basal and cytokine-mediated myelopoiesis. Int J Mol Sci. 2023. https://doi.org/10.3390/ijms241612757.CrossRefPubMedPubMedCentral

51.

Lv J, Qin L, Zhao R, Wu D, Wu Z, Zheng D, et al. Disruption of CISH promotes the antitumor activity of human T cells and decreases PD-1 expression levels. Mol Ther Oncolytics. 2022. https://doi.org/10.1016/j.omto.2022.12.003.CrossRefPubMedPubMedCentral

52.

Chabeda A, Yanez RJR, Lamprecht R, Meyers AE, Rybicki EP, Hitzeroth II. Therapeutic vaccines for high-risk HPV-associated diseases. Papillomavirus Res. 2018. https://doi.org/10.1016/j.pvr.2017.12.006.CrossRefPubMed

53.

Fakhr E, Modic Z, Cid-Arregui A. Recent developments in immunotherapy of cancers caused by human papillomaviruses. Immunology. 2021. https://doi.org/10.1111/imm.13285.CrossRefPubMed

54.

Inturi R, Jemth P. CRISPR/Cas9-based inactivation of human papillomavirus oncogenes E6 or E7 induces senescence in cervical cancer cells. Virology. 2021. https://doi.org/10.1016/j.virol.2021.07.005.CrossRefPubMed

55.

Hu Z, Ding W, Zhu D, Yu L, Jiang X, Wang X, et al. TALEN-mediated targeting of HPV oncogenes ameliorates HPV-related cervical malignancy. J Clin Invest. 2015. https://doi.org/10.1172/JCI78206.CrossRefPubMedPubMedCentral

56.

Tang L, Huang Z, Mei H, Hu Y. Immunotherapy in hematologic malignancies: achievements, challenges and future prospects. Signal Transduct Target Ther. 2023. https://doi.org/10.1038/s41392-023-01521-5.CrossRefPubMedPubMedCentral

57.

Fenton GA, Mitchell DA. Cellular Cancer Immunotherapy Development and Manufacturing in the clinic. Clin Cancer Res. 2023. https://doi.org/10.1158/1078-0432.CCR-22-2257.CrossRefPubMed

58.

Asmamaw Dejenie T, Tiruneh G, Medhin M, Dessie Terefe G, Tadele Admasu F, Wale Tesega W, Chekol Abebe E. Current updates on generations, approvals, and clinical trials of CAR T-cell therapy. Hum Vaccin Immunother. 2022. https://doi.org/10.1080/21645515.2022.2114254.CrossRefPubMedPubMedCentral

59.

Tang HKC, Wang B, Tan HX, Sarwar MA, Baraka B, Shafiq T, et al. CAR T-Cell therapy for Cancer: latest updates and challenges, with a focus on B-Lymphoid malignancies and selected solid tumours. Cells. 2023. https://doi.org/10.3390/cells12121586.CrossRefPubMedPubMedCentral

60.

Sadelain M, Brentjens R, Riviere I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013. https://doi.org/10.1158/2159-8290.CD-12-0548.CrossRefPubMedPubMedCentral

61.

Di Stasi A, Tey S, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011. https://doi.org/10.1056/NEJMoa1106152.CrossRefPubMedPubMedCentral

62.

Guercio M, Manni S, Boffa I, Caruso S, Di Cecca S, Sinibaldi M, et al. Inclusion of the Inducible Caspase 9 suicide gene in CAR Construct increases Safety of CAR.CD19 T cell therapy in B-Cell malignancies. Front Immunol. 2021. https://doi.org/10.3389/fimmu.2021.755639.CrossRefPubMedPubMedCentral

63.

Baker DJ, Arany Z, Baur JA, Epstein JA, June CH. CAR T therapy beyond cancer: the evolution of a living drug. Nature. 2023. https://doi.org/10.1038/s41586-023-06243-w.CrossRefPubMedPubMedCentral

64.

Wang X, Riviere I. Clinical manufacturing of CAR T cells: foundation of a promising therapy. Mol Ther Oncolytics. 2016. https://doi.org/10.1038/mto.2016.15.CrossRefPubMedPubMedCentral

65.

Blache U, Popp G, Dunkel A, Koehl U, Fricke S. Potential solutions for manufacture of CAR T cells in cancer immunotherapy. Nat Commun. 2022. https://doi.org/10.1038/s41467-022-32866-0.CrossRefPubMedPubMedCentral

66.

Yan T, Zhu L, Chen J. Current advances and challenges in CAR T-Cell therapy for solid tumors: tumor-associated antigens and the tumor microenvironment. Exp Hematol Oncol. 2023. https://doi.org/10.1186/s40164-023-00373-7.CrossRefPubMedPubMedCentral

67.

Mount CW, Majzner RG, Sundaresh S, Arnold EP, Kadapakkam M, Haile S, et al. Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M(+) diffuse midline gliomas. Nat Med. 2018. https://doi.org/10.1038/s41591-018-0006-x.CrossRefPubMedPubMedCentral

68.

de Billy E, Pellegrino M, Orlando D, Pericoli G, Ferretti R, Businaro P, et al. Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant. Neuro Oncol. 2022. https://doi.org/10.1093/neuonc/noab300.CrossRefPubMedPubMedCentral

69.

Del Baldo G, Del Bufalo F, Pinacchio C, Carai A, Quintarelli C, De Angelis B, et al. The peculiar challenge of bringing CAR-T cells into the brain: perspectives in the clinical application to the treatment of pediatric central nervous system tumors. Front Immunol. 2023. https://doi.org/10.3389/fimmu.2023.1142597.CrossRefPubMedPubMedCentral

70.

Majzner RG, Ramakrishna S, Yeom KW, Patel S, Chinnasamy H, Schultz LM, et al. GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature. 2022. https://doi.org/10.1038/s41586-022-04489-4.CrossRefPubMedPubMedCentral

71.

Gargett T, Ebert LM, Truong NTH, Kollis PM, Sedivakova K, Yu W, et al. GD2-targeting CAR-T cells enhanced by transgenic IL-15 expression are an effective and clinically feasible therapy for glioblastoma. J Immunother Cancer. 2022. https://doi.org/10.1136/jitc-2022-005187.CrossRefPubMedPubMedCentral

72.

Del Bufalo F, De Angelis B, Caruana I, Del Baldo G, De Ioris MA, Serra A, et al. GD2-CART01 for relapsed or Refractory High-Risk Neuroblastoma. N Engl J Med. 2023. https://doi.org/10.1056/NEJMoa2210859.CrossRefPubMed

73.

Abou-El-Enein M, Elsallab M, Feldman SA, Fesnak AD, Heslop HE, Marks P, et al. Scalable Manufacturing of CAR T cells for Cancer Immunotherapy. Blood Cancer Discov. 2021. https://doi.org/10.1158/2643-3230.BCD-21-0084.CrossRefPubMedPubMedCentral

74.

Tyagarajan S, Spencer T, Smith J, Optimizing CAR-T. Cell Manufacturing processes during pivotal clinical trials. Mol Ther Methods Clin Dev. 2019. https://doi.org/10.1016/j.omtm.2019.11.018.CrossRefPubMedPubMedCentral

75.

Wagner DL, Koehl U, Chmielewski M, Scheid C, Stripecke R, Review. Sustainable clinical development of CAR-T cells - switching from viral transduction towards CRISPR-Cas Gene Editing. Front Immunol. 2022. https://doi.org/10.3389/fimmu.2022.865424.CrossRefPubMedPubMedCentral

76.

Wei Z, Xu J, Zhao C, Zhang M, Xu N, Kang L, et al. Prediction of severe CRS and determination of biomarkers in B cell-acute lymphoblastic leukemia treated with CAR-T cells. Front Immunol. 2023. https://doi.org/10.3389/fimmu.2023.1273507.CrossRefPubMedPubMedCentral

77.

Quintarelli C, Guercio M, Manni S, Boffa I, Sinibaldi M, Di Cecca S, et al. Strategy to prevent epitope masking in CAR.CD19 + B-cell leukemia blasts. J Immunother Cancer. 2021. https://doi.org/10.1136/jitc-2020-001514.CrossRefPubMedPubMedCentral

78.

Locatelli F, Shah B, Thomas T, Velasco K, Adedokun B, Aldoss I, et al. Incidence of CD19-negative relapse after CD19-targeted immunotherapy in R/R BCP acute lymphoblastic leukemia: a review. Leuk Lymphoma. 2023. https://doi.org/10.1080/10428194.2023.2232496.CrossRefPubMed

79.

Ghaffari S, Khalili N, Rezaei N. CRISPR/Cas9 revitalizes adoptive T-cell therapy for cancer immunotherapy. J Exp Clin Cancer Res. 2021. https://doi.org/10.1186/s13046-021-02076-5.CrossRefPubMedPubMedCentral

80.

Ning L, Xi J, Zi Y, Chen M, Zou Q, Zhou X, et al. Prospects and challenges of CRISPR/Cas9 gene-editing technology in cancer research. Clin Genet. 2023. https://doi.org/10.1111/cge.14424.CrossRefPubMed

81.

Dimitri A, Herbst F, Fraietta JA. Engineering the next-generation of CAR T-cells with CRISPR-Cas9 gene editing. Mol Cancer. 2022. https://doi.org/10.1186/s12943-022-01559-z.CrossRefPubMedPubMedCentral

82.

Mueller KP, Piscopo NJ, Forsberg MH, Saraspe LA, Das A, Russell B, et al. Production and characterization of virus-free, CRISPR-CAR T cells capable of inducing solid tumor regression. J Immunother Cancer. 2022. https://doi.org/10.1136/jitc-2021-004446.CrossRefPubMedPubMedCentral

83.

Li L, Hu S, Chen X. Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities. Biomaterials. 2018. https://doi.org/10.1016/j.biomaterials.2018.04.031.CrossRefPubMedPubMedCentral

84.

Balke-Want H, Keerthi V, Cadinanos-Garai A, Fowler C, Gkitsas N, Brown AK, et al. Non-viral chimeric antigen receptor (CAR) T cells going viral. Immunooncol Technol. 2023. https://doi.org/10.1016/j.iotech.2023.100375.CrossRefPubMedPubMedCentral

85.

Liu X, Zhang Y, Cheng C, Cheng AW, Zhang X, Li N, et al. CRISPR-Cas9-mediated multiplex gene editing in CAR-T cells. Cell Res. 2017. https://doi.org/10.1038/cr.2016.142.CrossRefPubMedPubMedCentral

86.

Hu Y, Zhou Y, Zhang M, Ge W, Li Y, Yang L, et al. CRISPR/Cas9-Engineered Universal CD19/CD22 Dual-targeted CAR-T cell therapy for Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia. Clin Cancer Res. 2021. https://doi.org/10.1158/1078-0432.CCR-20-3863.CrossRefPubMedPubMedCentral

87.

Henia Dar D, Henderson Z, Padalia MS, Ashley Porras D, Mu MS, Maeng Kyungah. PhD, Seshidhar Police, PhD, Demetrios Kalaitzidis, PhD, Jonathan Terrett, PhD, Jason Sagert, PhD. Preclinical Development of CTX120, an allogeneic CAR-T cell targeting Bcma. 2018;132.

88.

Sumanta K, Pal MD, Tran B, Haanen MBBSFRACPJB, PhD3 MD, Hurwitz M, PhD4 MD, Sacher A, Argawal MDN, Tannir MDN, Elizabeth Budde MDL, Harrison MDS, PhD MBBS, Klobuch FRACPS, MD, Patel SS, Karsten V, Srour SA. PhD9, Kaitlyn Cohen, MS8, Ellen B. Gurary, PhD8, Henia Dar, PhD8, Anna Ma, MS8, Anjali Sharma, MD8, MD7. 558 CTX130 allogeneic CRISPR-Cas9–engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: results from the phase 1 COBALT-RCC study. 2022.

Title: GMP-manufactured CRISPR/Cas9 technology as an advantageous tool to support cancer immunotherapy
Authors: M Caforio
S Iacovelli
C Quintarelli
F Locatelli
Valentina Folgiero
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Cancer Therapy
Cancer Immunotherapy
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2024
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-024-02993-1

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Main body

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2024

Colorectal carcinoma peritoneal metastases-derived organoids: results and perspective of a model for tailoring hyperthermic intraperitoneal chemotherapy from bench-to-bedside

Tight junction protein cingulin variant is associated with cancer susceptibility by overexpressed IQGAP1 and Rac1-dependent epithelial-mesenchymal transition

Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery

Unveiling the gastric microbiota: implications for gastric carcinogenesis, immune responses, and clinical prospects

PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility

Correction: c-Myc-activated long non-coding RNA LINC01050 promotes gastric cancer growth and metastasis by sponging miR-7161-3p to regulate SPZ1 expression

Keynote webinar | Spotlight on antibody–drug conjugates in cancer