Collection of Large-scale Expanded Lymphocyte Cultures for Adoptive Immunotherapy Using a COBE Spectra Apheresis Machine

Schallmach, Ester; Sareli, Rina; Besser, Michal J.; Leipsiger, Shai; Hardan, Izhar; Treves, Abraham J.; Nagler, Arnon; Schachter, Jacob

doi:10.1097/cji.0b013e318175f66b

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…On day 14 of the large-scale expansion, culture medium was reduced drastically by using a COBE Spectra apheresis machine (Gambro BCT; ref. 22) and the cells were infused into the lympho-depleted patient by i.v. administration.…”

Section: Translational Relevancementioning

confidence: 99%

Clinical Responses in a Phase II Study Using Adoptive Transfer of Short-term Cultured Tumor Infiltration Lymphocytes in Metastatic Melanoma Patients

Besser

Shapira‐Frommer

Treves

et al. 2010

Clinical Cancer Research

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Purpose: Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) has shown promising results in metastatic melanoma patients. Although objective response rates of over 50% have been reported, disadvantages of this approach are the labor-intensive TIL production and a very high drop-out rate of enrolled patients, limiting its widespread applicability.Previous studies showed a clear correlation between short TIL culture periods and clinical response. Therefore, we used a new TIL production technique using unselected, minimally cultured, bulk TIL (Young-TIL). The use of Young-TIL is not restricted to human leukocyte antigen (HLA)-A2 patients.The purpose of this study is to explore the efficacy and toxicity of adoptively transferred Young-TIL following lympho-depleting chemotherapy in metastatic melanoma patients, refractory to interleukin-2 and chemotherapy.Experimental Design: Young-TIL cultures for 90% of the patients were successfully generated, enabling the treatment of most enrolled patients. We report here the results of 20 evaluated patients.Results: Fifty percent of the patients achieved an objective clinical response according to the Response Evaluation Criteria in Solid Tumors, including two ongoing complete remissions (20+, 4+ months) and eight partial responses (progression-free survival: 18+, 13+, 10+, 9, 6+, 4, 3+, and 3 months). All responders are currently alive. Four additional patients showed disease stabilization. Side effects were transient and manageable.Conclusion: We showed that lympho-depleting chemotherapy followed by transfer of short-term cultured TIL can mediate tumor regression in 50% of metastatic melanoma with manageable toxicity. The convincing clinical results combined with the simplification of the process may thus have a major effect on cell therapy of cancer. Clin Cancer Res; 16(9); 2646-55. ©2010 AACR.

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Section: Translational Relevancementioning

confidence: 99%

Clinical Responses in a Phase II Study Using Adoptive Transfer of Short-term Cultured Tumor Infiltration Lymphocytes in Metastatic Melanoma Patients

Besser

Shapira‐Frommer

Treves

et al. 2010

Clinical Cancer Research

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409

374

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“…For this purpose we developed a novel efficient process based on the COBE Spectra apheresis machine usually employed for apheresis process and widely used at medical centers. 24 The cells were immediately infused into the lympho-depleted patient by intravenous administration over 30 minutes.…”

Section: Til Rapid Expansionmentioning

confidence: 99%

Minimally Cultured or Selected Autologous Tumor-infiltrating Lymphocytes After a Lympho-depleting Chemotherapy Regimen in Metastatic Melanoma Patients

Besser¹,

Shapira‐Frommer²,

Treves

et al. 2009

Journal of Immunotherapy

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111

114

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Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression in half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated with "Selected"-TIL, as previously reported and 8 patients with the modified version of "Young"-TIL. Selected-TIL protocol required the establishment of multiple T-cell cultures from 1 patient and in vitro selection of cultures secreting interferon-gamma upon antigenic stimulation. In contrast, Young-TIL are minimally cultured T cells with superior in vitro features that do not require further selection. Two of 12 Selected-TIL patients experienced objective clinical responses (1 complete response, 1 partial response). Out of 8 treated Young-TIL patients, 1 experienced complete response, 2 partial response, and 4 patients had disease stabilization. Twenty-one of 33 enrolled Selected-TIL patients were excluded from the protocol, mainly as cultures failed the interferon-gamma selection criteria or due to clinical deterioration, compared with only 3 Young-TIL patients. Expected bone marrow suppression and high-dose IL-2 toxicity were transient. There was no treatment-related mortality. This study vindicates the feasibility and effectiveness of TIL technology and calls for further efforts to implement and enhance this modality. The use of minimally cultured, unselected Young-TIL enables the treatment of most enrolled patients. Although the cohort of Young-TIL patients treated so far is rather small and the follow-up short, the response rate is encouraging.

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“…Unselected TIL cultures were further expanded ex vivo to treatment levels in a 14-day rapid expansion procedure (REP) using anti-CD3 antibody (Orthoclone OKT3, Janssen-Cilag: Johnson and Johnson, New Brunswick,NJ USA 3,000 IU/mL rhIL-2 and irradiated feeder cells as previously described (24,25). On the day of infusion, reduction of the culture medium volume was performed using a COBE Spectra apheresis machine (COBE Laboratories Inc. Lakewood, CO, USA) (26).…”

Section: Tissue Resection and Tils Harvestingmentioning

confidence: 99%

Tissue Harvesting for Adoptive Tumor Infiltrating Lymphocyte Therapy in Metastatic Melanoma

et al. 2019

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Background/Aim: Adoptive transfer of tumorinfiltrating lymphocytes (TILs) combined with nonmyeloablative chemotherapy (NMA) has been shown to prolong survival in patients with metastatic disease. Materials and Methods: Tissue harvesting was performed form a variety of sites. TILs were isolated, expanded and infused with bolus high-dose IL-2. Results: Between 2008 and 2018, 242 lesions were resected for TILs harvesting from a range of sites form 196 patients without mortality and with minimal morbidity. Of those harvested, 75 were unable to complete therapy because of clinical deterioration during the wait period. Of 121 evaluable treated patients, there was no effect of metastatic site biopsied on the mean fold TIL expansion. Those receiving prior ipilimumab had a higher TIL fold expansion but a lower TIL fold expansion than those exposed to anti-PD1 therapy. Conclusion: Harvesting may be safely performed with successful TIL expansion from most sites. Prior check point inhibitory immunotherapy may potentially influence TIL fold expansion.

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Collection of Large-scale Expanded Lymphocyte Cultures for Adoptive Immunotherapy Using a COBE Spectra Apheresis Machine

Cited by 7 publications

References 21 publications

Clinical Responses in a Phase II Study Using Adoptive Transfer of Short-term Cultured Tumor Infiltration Lymphocytes in Metastatic Melanoma Patients

Clinical Responses in a Phase II Study Using Adoptive Transfer of Short-term Cultured Tumor Infiltration Lymphocytes in Metastatic Melanoma Patients

Minimally Cultured or Selected Autologous Tumor-infiltrating Lymphocytes After a Lympho-depleting Chemotherapy Regimen in Metastatic Melanoma Patients

Tissue Harvesting for Adoptive Tumor Infiltrating Lymphocyte Therapy in Metastatic Melanoma

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