Toward “off‐the‐shelf” allogeneic CAR T cells

Aftab, Blake T.; Sasu, Barbra J.; Krishnamurthy, Janani; Gschweng, Eric H.; Alcazer, Vincent; Depil, Stéphane

doi:10.1002/acg2.86

Cited by 23 publications

(24 citation statements)

References 84 publications

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“…Two major categories of such allogeneic cell products are based on engineering healthy-donor-derived conventional ab T cells or NK cells. 14,68,69,77 Because conventional ab T cells risk inducing GvHD in allogeneic hosts due to HLA incompatibility, these T cells need to be gene edited to ablate endogenous TCR expression, usually by disrupting the TRAC or/and TRBC gene loci, to make them suitable for allogeneic cell therapy but meanwhile may also potentially increase manufacture complexity. [10][11][12][13] On the other hand, NK-based allogeneic cell products are considered of low GvHD risk and therefore do not require additional gene editing, but their in vivo clonal expansion and antitumor performance may be limited compared to that of conventional ab T cells.…”

Section: Discussionmentioning

confidence: 99%

Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy

Zhou

Kim

et al. 2021

Cell Reports Medicine

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Section: Discussionmentioning

confidence: 99%

Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy

Zhou

Kim

et al. 2021

Cell Reports Medicine

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“…Healthy donors can be selected based on T‐cell fitness and on successful and consistent manufacturability, ensuring that eligible R/R B‐cell NHL patients have immediate access to a high‐quality and uniform CAR T‐cell product. 1 , 2 , 3 , 4 , 5 Challenges do exist with allogeneic CAR T‐cell products, namely graft‐versus‐host disease (GvHD) and immunogenicity (i.e. host‐versus‐graft rejection) of the allogeneic CAR T‐cell product, both of which are consequences of human leucocyte antigen (HLA) incompatibility between donors and patients.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic CD20‐targeted γδ T cells exhibit innate and adaptive antitumor activities in preclinical B‐cell lymphoma models

et al. 2022

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ObjectivesAutologous chimeric antigen receptor (CAR) αβ T‐cell therapies have demonstrated remarkable antitumor efficacy in patients with haematological malignancies; however, not all eligible cancer patients receive clinical benefit. Emerging strategies to improve patient access and clinical responses include using premanufactured products from healthy donors and alternative cytotoxic effectors possessing intrinsic tumoricidal activity as sources of CAR cell therapies. γδ T cells, which combine innate and adaptive mechanisms to recognise and kill malignant cells, are an attractive candidate platform for allogeneic CAR T‐cell therapy. Here, we evaluated the manufacturability and functionality of allogeneic peripheral blood‐derived CAR+ Vδ1 γδ T cells expressing a second‐generation CAR targeting the B‐cell‐restricted CD20 antigen.MethodsDonor‐derived Vδ1 γδ T cells from peripheral blood were ex vivo‐activated, expanded and engineered to express a novel anti‐CD20 CAR. In vitro and in vivo assays were used to evaluate CAR‐dependent and CAR‐independent antitumor activities of CD20 CAR+ Vδ1 γδ T cells against B‐cell tumors.ResultsAnti‐CD20 CAR+ Vδ1 γδ T cells exhibited innate and adaptive antitumor activities, such as in vitro tumor cell killing and proinflammatory cytokine production, in addition to in vivo tumor growth inhibition of B‐cell lymphoma xenografts in immunodeficient mice. Furthermore, CD20 CAR+ Vδ1 γδ T cells did not induce xenogeneic graft‐versus‐host disease in immunodeficient mice.ConclusionThese preclinical data support the clinical evaluation of ADI‐001, an allogeneic CD20 CAR+ Vδ1 γδ T cell, and a phase 1 study has been initiated in patients with B‐cell malignancies (NCT04735471).

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“…The logistics involved in this traditional manufacturing and treatment with autologous CAR-T cells adds complexity for clinicians and patients because the period in between, referred to as “vein-to-vein time” , ranges between three and 4 weeks in developed countries. This period can be daunting for the patients awaiting treatment and renders the CAR-T treatment complicated for patients with rapidly progressing diseases ( Aftab et al, 2020 ). Nowadays, this therapy presents these main manufacturing challenges and the picture in developed and underdeveloped countries is very different.…”

Section: Immunotherapy a New Approach For Cancer Treatmentmentioning

confidence: 99%

“…CAR-T cells manufacturing does not allow volumetric scale-up, consequently, cells must be prepared as a single batch limiting the quantity of available product. Under this scenario, patients may not have the opportunity to receive a new infusion of their CAR-T cells quickly and easily if needed ( Aftab et al, 2020 ; Papathanasiou et al, 2020 ).…”

Section: Immunotherapy a New Approach For Cancer Treatmentmentioning

confidence: 99%

Chimeric Antigen Receptor-T Cells: A Pharmaceutical Scope

et al. 2021

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Cancer is among the leading causes of death worldwide. Therefore, improving cancer therapeutic strategies using novel alternatives is a top priority on the contemporary scientific agenda. An example of such strategies is immunotherapy, which is based on teaching the immune system to recognize, attack, and kill malignant cancer cells. Several types of immunotherapies are currently used to treat cancer, including adoptive cell therapy (ACT). Chimeric Antigen Receptors therapy (CAR therapy) is a kind of ATC where autologous T cells are genetically engineered to express CARs (CAR-T cells) to specifically kill the tumor cells. CAR-T cell therapy is an opportunity to treat patients that have not responded to other first-line cancer treatments. Nowadays, this type of therapy still has many challenges to overcome to be considered as a first-line clinical treatment. This emerging technology is still classified as an advanced therapy from the pharmaceutical point of view, hence, for it to be applied it must firstly meet certain requirements demanded by the authority. For this reason, the aim of this review is to present a global vision of different immunotherapies and focus on CAR-T cell technology analyzing its elements, its history, and its challenges. Furthermore, analyzing the opportunity areas for CAR-T technology to become an affordable treatment modality taking the basic, clinical, and practical aspects into consideration.

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Toward “off‐the‐shelf” allogeneic CAR T cells

Cited by 23 publications

References 84 publications

Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy

Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy

Allogeneic CD20‐targeted γδ T cells exhibit innate and adaptive antitumor activities in preclinical B‐cell lymphoma models

Chimeric Antigen Receptor-T Cells: A Pharmaceutical Scope

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