Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. VIII: CAR-T cells: preclinical development - Safety and efficacy evaluation

Picanço-Castro, Virginia; Bonamino, Martín Hernan; Ramos, Rodrigo Nalio; Guerino-Cunha, Renato L; Oliveira, Theo Gremen M; Rego, Eduardo M

doi:10.1016/j.htct.2021.09.008

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Hematology, Transfusion and Cell Therapy

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Sumário

Special article • Hematol., Transfus. Cell Ther. 43 (suppl 2) • 2021 • https://doi.org/10.1016/j.htct.2021.09.008 copy

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. VIII: CAR-T cells: preclinical development - Safety and efficacy evaluation

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Currently, there are four CAR-T products commercially available on the market. CAR-T cells have shown high remission rates and they represent an effective treatment option for patients with resistant or refractory B cell malignancies. Approval of these cell therapy products came after an extended period of preclinical evaluation that demonstrated unprecedented efficacy in this difficult-to-treat patient population. This review article outlines the main preclinical evaluations needed for CAR T cell product development.

Keywords:
Immunotherapy; Chimeric antigen receptor; Adoptive cell therapy; Preclinical studies; Advanced cell therapy

	Viral vectors				Non viral vectors
	Lentiviral vector	Retroviral vector	Adenovirus vector	Adeno-associated virus vector	Transposon	mRNA	CRISPR/Cas9
Infected cells	Dividing and quiescent cells	Dividing cells	Dividing and quiescent cells	Dividing and quiescent cells	Dividing cells	Dividing cells	Dividing cells
Large transgene capacity	No	No	No	No	Yes	Yes	Yes
Safe and well tolerated clinical studies	Most used now				Less used, but with great potential
Permanent modification of the cells	Yes	Yes	No	Yes	Yes	No	Yes
IP protection	✓ ✓ ✓	✓ ✓	✓ ✓	✓ ✓	✓ ✓ ✓	✓ ✓ ✓ ✓	✓ ✓ ✓ ✓
Cost of production	Costly and laborious				Cheap and simple
Advantages	High efficiency				Cheap High efficiency	No integration on risks, Cheaper than virus product	Precise gene insertion Don't need exogenous promoter
Disadvantage	Risk of insertional mutagenesis					Transient expression	Expense Low efficiency Potential off targets

Soluble cytokines and chemokines categories
Effector	Stimulatory	Regulatory	Inflammatory	Chemoattractive
granzyme-B, IFN-gamma, MIP-1alpha, perforin, TNF-alpha, TNF-beta	GM-CSF, IL-2, IL-5, IL-7, IL-8, IL-9, IL-12, IL-15, IL-21	IL-4, IL-10, IL-13, IL-22, TGF-beta1, sCD137, sCD40L	IL-1B, IL-6, IL-17A, IL-17F, MCP-1, MCP-4	CCL-11, IP-10, MIP-1beta, RANTES

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH) R. Dr. Diogo de Faria, 775 cj 133, 04037-002, São Paulo / SP - Brasil - São Paulo - SP - Brazil
E-mail: htct@abhh.org.br

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[1] * Corresponding author at: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HCFMRP USP), Ribeirão Preto, SP, Brazil. E-mail address: emrego@hcrp.fmrp.usp.br (E.M. Rego).