Effect of anti-CD3 antibody on the generation of interleukin-2-activated lymphocytes from tumor tissues of gastrointestinal cancer

Ohta, Tomohiko; Kikuchi, Hiroe; Ogata, Haruki; Iwata, Kunihiro; Yoshida, Katsumi; Kono, Kenji; Watanabe, Hiroshi

doi:10.1002/1097-0142(19920815)70:4<741::aid-cncr2820700405>3.0.co;2-5

Cited by 3 publications

(1 citation statement)

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“…Recent evidence demonstrates that T-cells isolated from tumor-infiltrating lymph nodes express higher levels of markers associated with cellular “exhaustion” (apoptosis genes, CTLA-4) which may partly explain the limited ability to generate TIL from some patients and efficacy in less than half the patients treated (38). Nonetheless, similar attempts to isolate TIL from other solid tumors are currently under investigation (39-44). …”

Section: Introductionmentioning

confidence: 99%

Current translational and clinical practices in hematopoietic cell and gene therapy

DiGiusto

Kiem

2012

Cytotherapy

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Clinical trials over the last 15 years have demonstrated that cell and gene therapy for cancer, monogenic and infectious disease is feasible and can lead to long-term benefit for patients (1). These trials however have been limited to proof of principle and were conducted on modest numbers of patients or over long periods of time. In order for these studies to move towards standard practice and commercialization, scalable technologies for the isolation, ex vivo manipulation and delivery of these cells to patients must be developed. Additionally, regulatory strategies and clinical protocols for the collection, creation and delivery of cell products must be generated. In this article we will review recent progress in hematopoietic cell and gene therapy, describe some of the current issues facing the field and discuss clinical, technical and regulatory approaches used to navigate the road to product development.

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Section: Introductionmentioning

confidence: 99%

Current translational and clinical practices in hematopoietic cell and gene therapy

DiGiusto

Kiem

2012

Cytotherapy

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Lymphatic system of the pancreas

O’Morchoe

1997

Microsc. Res. Tech.

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Injury to Autologous Normal Tissues and Tumors Mediated by Lymphokine-Activated Killer (LAK) Cells Generated In Vitro from Peripheral Blood Mononuclear Cells of Glioblastoma Patients

Fujimiya

Suzuki²,

Katakura³

et al. 1999

Journal of Hematotherapy

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Activation of peripheral blood mononuclear cells (PBMC) with IL-2 generates lymphokine-activated killer (LAK) cells that show a broad target cell range. In adoptive immunotherapy using in vitro-generated LAK cells, the intensity and specificity of their cytotoxic activity affect the prognosis of cancer patients. The present study was designed to examine the tumor-specific spectrum of T lymphocytes generated from the PBMC of patients with recurrent glioblastoma by in vitro propagation with IL-2 plus either soluble or solid-phase anti-CD3 monoclonal antibody (MAb) in short-term or long-term cultures. Both short-term and long-term culturing with solid-phase anti-CD3 MAb plus IL-2 yielded broad-reactivity CD8+ alphabetaT and gammadeltaT lymphocytes, both of which were non-MHC restricted, as shown by the fact that they were able to lyse autologous glioblastoma cells, MHC class I+II- allogeneic glioblastoma cells, and MHC class I-II-NK-sensitive K562 target cells. More importantly, these cells from patients failed to lyse fresh autologous PBMC. These results demonstrate that cells generated using this approach are non-MHC-restricted LAK cells and exhibit marked tumor specificity. In contrast, incubation with soluble anti-CD3 MAb generated T lymphocytes that after long-term culture, were either CD4+ or CD8+. These caused significant lysis of both allogeneic and autologous glioblastoma target cells, the extent of lysis being greater than that using cells produced by culturing with the solid-phase MAb. However, both the CD4+ and CD8+ cells also caused greater lysis of autologous normal PBMC, indicating that cells generated using this approach may cause significant adverse reactions in cancer patients if used for immunotherapy.

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Effect of anti-CD3 antibody on the generation of interleukin-2-activated lymphocytes from tumor tissues of gastrointestinal cancer

Cited by 3 publications

References 17 publications

Current translational and clinical practices in hematopoietic cell and gene therapy

Current translational and clinical practices in hematopoietic cell and gene therapy

Lymphatic system of the pancreas

Injury to Autologous Normal Tissues and Tumors Mediated by Lymphokine-Activated Killer (LAK) Cells Generated In Vitro from Peripheral Blood Mononuclear Cells of Glioblastoma Patients

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