Simplified protocol for clinical-grade tumor-infiltrating lymphocyte manufacturing with use of the Wave bioreactor

Donia, Marco; Larsen, Signe Møllebæk; Met, Özcan; Svane, Inge Marie

doi:10.1016/j.jcyt.2014.02.004

Cited by 49 publications

(51 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…26) and a dynamic expansion in REP (27). TIL microcultures from all fragments were pooled to one bulk culture, according to the "young TIL" method (28,29) and the pooled pre-REP TIL culture was either cryopreserved or entered directly into the REP.…”

Section: Generation Of Tilmentioning

confidence: 99%

“…TIL microcultures from all fragments were pooled to one bulk culture, according to the "young TIL" method (28,29) and the pooled pre-REP TIL culture was either cryopreserved or entered directly into the REP. Approximately, 20 Â 10 6 cells were used to initiate the REP, during which the TILs were expanded to therapeutic levels in a large scale expansion procedure with the Wave Bioreactor 2/10 system (GE Healthcare) as described previously (27). At day 14, the cells were harvested and transferred to an infusion bag in a suspension of 250 mL sodium chloride with 2.5% albumin and 300 IU/mL IL2.…”

Section: Generation Of Tilmentioning

confidence: 99%

See 1 more Smart Citation

Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen

Andersen

Donia

Ellebæk

et al. 2016

Clinical Cancer Research

Self Cite

244

206

View full text Add to dashboard Cite

Purpose: Adoptive cell transfer therapy (ACT) based on autologous tumor-infiltrating lymphocytes (TIL) has achieved impressive clinical results in several phase I and II trials performed outside of Europe. Although transient, the toxicities associated with high-dose (HD) bolus IL2 classically administered together with TILs are severe. To further scrutinize whether similar results can be achieved with lower doses of IL2, we have carried out a phase I/II trial of TIL transfer after classical lymphodepleting chemotherapy followed by an attenuated IL2 regimen.Experimental Design: Twenty-five patients with progressive treatment-refractory metastatic melanoma, good clinical performance, age < 70 years, and at least one resectable metastasis were eligible. TIL infusion was preceded by standard lymphodepleting chemotherapy and followed by attenuated doses of IL2 administered in an intravenous, continuous decrescendo regimen (ClinicalTrials.gov Identifier: NCT00937625).Results: Classical IL2-related toxicities were observed but patients were manageable in a general oncology ward without the need for intervention from the intensive care unit. RECIST 1.0 evaluation displayed three complete responses and seven partial responses (ORR 42%). Median overall survival was 21.8 months. Tumor regression was associated with a higher absolute number of infused tumor-reactive T cells. Moreover, induction and persistence of antimelanoma T-cell responses in the peripheral blood was strongly correlated to clinical response to treatment.Conclusions: TIL-ACT with a reduced IL2 decrescendo regimen results in long-lasting complete responses in patients with treatment-refractory melanoma. Larger randomized trials are needed to elucidate whether clinical efficacy is comparable with TIL-ACT followed by HD bolus IL2.

show abstract

Section: Generation Of Tilmentioning

confidence: 99%

Section: Generation Of Tilmentioning

confidence: 99%

Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen

Andersen

Donia

Ellebæk

et al. 2016

Clinical Cancer Research

Self Cite

244

206

View full text Add to dashboard Cite

show abstract

“…Notably, we have observed a considerable increase in expansion rate up to more than 5.000-fold using this system [30].…”

Section: Til Preparation Proceduresmentioning

confidence: 64%

“…To this end, CCIT has established a practical and simplified protocol of TIL manufacturing using a closed system bioreactor. This protocol will ensure higher applicability of TIL production in laboratory routine, reducing work load while still allowing the generation of high-quality TIL products [30].…”

Section: Dissemination Of Til-based Act To Multiple Centersmentioning

confidence: 99%

Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma: what is needed to achieve standard of care?

Svane

Verdegaal

2014

Cancer Immunol Immunother

Self Cite

View full text Add to dashboard Cite

Adoptive cell therapy (ACT) based on autologous T cell derived either from tumor as tumor-infiltrating lymphocytes (TILs) or from peripheral blood is developing as a key area of future personalized cancer therapy. TIL-based ACT is defined as the infusion of T cells harvested from autologous fresh tumor tissues after ex vivo activation and extensive expansion. TIL-based ACT has so far only been tested in smaller phase I/II studies, but these studies consistently confirm an impressive clinical response rate of up to 50 % in metastatic melanoma including a significant proportion of patients with durable complete tumor eradication. These remarkable results justify the need for a definitive phase III trial documenting the efficacy of this type of T cell-based Advanced Therapy Medicinal Product in order to pave the way for regulatory approval and implementation of TIL therapy as a new treatment standard in oncology practice. TIL-based ACT can, however, only be offered to a limited group of patients based on the need for accessible tumor tissue, the complexity of TIL production procedures, and the very intensive nature of this three-step treatment including both high-dose chemotherapy and interleukin-2 in addition to T cell infusion. To this end, adoptive T cell therapy using peripheral blood mononuclear cell-derived T cells could be a welcome alternative to circumvent these limitations and broaden up the applicability of ACT. Here, we discuss current initiatives in this focused research review.

show abstract

“…Of these 17 patients, 6 patients received T cells that were generated by mixed lymphocyte tumor cultures of autologous tumor cells and peripheral blood mononuclear cells (22). The other 11 patients received T cells that were generated by rapid expansion of TILs (23). Within the ACT-treated group of 17 patients, 10 were classified as having CB (3Â SD, 4Â PR, and 3Â CR).…”

Section: Patient Characteristicsmentioning

confidence: 99%

Long-term Survival and Clinical Benefit from Adoptive T-cell Transfer in Stage IV Melanoma Patients Is Determined by a Four-Parameter Tumor Immune Signature

Melief

Visconti

Visser

et al. 2017

Cancer Immunology Research

View full text Add to dashboard Cite

The presence of tumor-infiltrating immune cells is associated with longer survival and a better response to immunotherapy in early-stage melanoma, but a comprehensive study of the in situ immune microenvironment in stage IV melanoma has not been performed. We investigated the combined influence of a series of immune factors on survival and response to adoptive cell transfer (ACT) in stage IV melanoma patients. Metastases of 73 stage IV melanoma patients, 17 of which were treated with ACT, were studied with respect to the number and functional phenotype of lymphocytes and myeloid cells as well as for expression of galectins-1, -3, and -9. Single factors associated with better survival were identified using Kaplan-Meier curves and multivariate Cox regression analyses, and those factors were used for interaction analyses. The results were validated using The Cancer Genome Atlas database. We identified four parameters that were associated with a better survival: CD8þ T cells, galectin-macrophage ratio, and the expression of galectin-3 by tumor cells. The presence of at least three of these parameters formed an independent positive prognostic factor for long-term survival. Patients displaying this four-parameter signature were found exclusively among patients responding to ACT and were the ones with sustained clinical benefit.

show abstract

Simplified protocol for clinical-grade tumor-infiltrating lymphocyte manufacturing with use of the Wave bioreactor

Cited by 49 publications

References 15 publications

Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen

Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen

Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma: what is needed to achieve standard of care?

Long-term Survival and Clinical Benefit from Adoptive T-cell Transfer in Stage IV Melanoma Patients Is Determined by a Four-Parameter Tumor Immune Signature

Contact Info

Product

Resources

About