Efficacy of single administration of tumor-infiltrating lymphocytes (TIL) in heavily pretreated patients with metastatic melanoma following checkpoint therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3045-3045 ◽  
Author(s):  
Amod Sarnaik ◽  
Harriet M. Kluger ◽  
Jason Alan Chesney ◽  
Jyothi Sethuraman ◽  
Anandharamen Veerapathran ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Metastatic Melanoma ◽  
Safety Profile ◽  
Ex Vivo ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Primary Objective ◽  
Braf Mutations ◽  
Best Response ◽  
Grade 3

3045 Background: Adoptive cell therapy with TIL involves collection of autologous lymphocytes from the tumor via surgical resection, ex vivo expansion of TIL, lymphodepletion of the patient prior to infusion of TIL using Fludarabine and Cyclophosphamide, followed by infusion of TIL. Up to 6 doses of IL-2 (600,000 IU/kg) is administered to support multiplication of TIL and engraftment. Here, we present the preliminary results from an ongoing, multi-site Phase 2 study of TIL for advanced metastatic melanoma. Methods: Patients with advanced metastatic melanoma who have failed at least one prior systemic therapy were enrolled. Primary objective of the study was to characterize safety profile of LN-144. At baseline, patients had a median age of 56 (41-72) years; 44% were ≥ 60 years old. Median sum of tumor diameters for the target lesions was 10.4 cm, and median of 3 prior therapies. All enlisted patients had prior anti-PD1 as well as anti-CTLA4 and 67% had received ≥ 3 prior therapies. Responses were assessed by RECIST 1.1. TIL products were centrally manufactured. No complications arose from shipment of tumors or TIL. Results: Results are presented through 31 Jan 2017 for the first 9 infused patients evaluable by two assessments. Eight of 9 patients received all 6 doses of IL-2 per protocol. The most common (≥3 patients) non-hematologic grade 3-4 TEAE was hypophosphatemia. No neurotoxicity of grade ≥ 3 was reported. There were no deaths or discontinuations due to SAEs related to study treatment. ORR was 33% (CR = 11%, PR = 22%, SD = 22%, PD = 33%, NE = 11%). Mean time to best response was 3.0 months and median duration of follow up was 3.6 months (1.1+, 12.1). Responses were observed in patients with tumors carrying wild type or BRAF mutations. All patients demonstrated persistence of TIL on day 14 post-infusion. Conclusions: Cell therapy with TIL is an effective treatment with acceptable safety profile for advanced metastatic melanoma patients who are refractory to anti-PD1. TIL products can be centrally manufactured for broad clinical application. This study will be expanded to enroll patients with a shorter manufacturing process as well as offering retreatment for study patients. Clinical trial information: NCT02360579.

scholarly journals Adoptive Cell Therapy for Patients With Metastatic Melanoma: Evaluation of Intensive Myeloablative Chemoradiation Preparative Regimens

2008 ◽  
Vol 26 (32) ◽  
pp. 5233-5239 ◽  
Author(s):  
Mark E. Dudley ◽  
James C. Yang ◽  
Richard Sherry ◽  
Marybeth S. Hughes ◽  
Richard Royal ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Metastatic Melanoma ◽  
Adoptive Cell Therapy ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Tumor Infiltrating Lymphocytes ◽  
Response Rates ◽  
Serum Levels ◽  
Autologous Tumor ◽  
Sequential Trials

Purpose The two approved treatments for patients with metastatic melanoma, interleukin (IL)-2 and dacarbazine, mediate objective response rates of 12% to 15%. We previously reported that adoptive cell therapy (ACT) with autologous antitumor lymphocytes in lymphodepleted hosts mediated objective responses in 51% of 35 patients. Here, we update that study and evaluate the safety and efficacy of two increased-intensity myeloablative lymphodepleting regimens. Patients and Methods We performed two additional sequential trials of ACT with autologous tumor-infiltrating lymphocytes (TIL) in patients with metastatic melanoma. Increasing intensity of host preparative lymphodepletion consisting of cyclophosphamide and fludarabine with either 2 (25 patients) or 12 Gy (25 patients) of total-body irradiation (TBI) was administered before cell transfer. Objective response rates by Response Evaluation Criteria in Solid Tumors (RECIST) and survival were evaluated. Immunologic correlates of effective treatment were studied. Results Although nonmyeloablative chemotherapy alone showed an objective response rate of 49%, when 2 or 12 Gy of TBI was added, the response rates were 52% and 72% respectively. Responses were seen in all visceral sites including brain. There was one treatment-related death in the 93 patients. Host lymphodepletion was associated with increased serum levels of the lymphocyte homeostatic cytokines IL-7 and IL-15. Objective responses were correlated with the telomere length of the transferred cells. Conclusion Host lymphodepletion followed by autologous TIL transfer and IL-2 results in objective response rates of 50% to 70% in patients with metastatic melanoma refractory to standard therapies.

The impact of checkpoint blockade prior to adoptive cell therapy using tumor-infiltrating lymphocytes for metastatic melanoma: An update from MD Anderson Cancer Center.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 138-138 ◽  
Author(s):  
Marie-Andree Forget ◽  
Cara L. Haymaker ◽  
Kenneth R. Hess ◽  
Jason Roszik ◽  
Scott Eric Woodman ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Metastatic Melanoma ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Checkpoint Blockade ◽  
High Dose ◽  
Autologous Tumor ◽  
Initial Report ◽  
Infiltrating Lymphocytes ◽  
The Impact

138 Background: Adoptive cell therapy (ACT) of autologous tumor-infiltrating lymphocytes (TIL) can produce long lasting treatment responses in patients (pts) with metastatic melanoma. In our initial report of 31 treated pts, we demonstrated overall response rate (ORR) of 48%. Due to the evolution of treatment options for metastatic melanoma with heavy reliance on immunomodulatory therapies, we sought to re-evaluate responses in the era of checkpoint blockade. Methods: Pts receive treatment consisting of 7 days of lymphodepleting chemotherapy consisting of cyclophosphamide and fludarabine. High dose interleukin-2 (720,000 IU/kg IV q 8 hrs up to 15 doses) was infused after TIL infusion. Responses were assessed by imaging per irRC. Results: A total of 74 pts have been treated in our initial TIL study with an updated ORR assessment of 43%. Stratification of pts according to their checkpoint blockade immune-modulator therapy prior to TIL ACT, demonstrated that prior Ipilimumab (Ipi) decreased ORR to 33% compared to 51% in checkpoint naïve pts and decreased overall survival (OS) post-TIL therapy (median 7.7 vs 24.6 months respectively). There were too few pts to assess the impact of anti-PD1 as a single agent. A multiparametric analysis revealed that LDH levels at the time of therapy mainly influences OS and ORR to TIL but still could not invalidate the impact of Ipi prior to TIL ACT. The durability of the response was also found to be different between the 2 groups (30% for Ipi prior and 50% No Ipi prior). This new reality also impacted previously reported parameters that correlated with ORR to TIL ACT such as the expression of B-and-T lymphocyte attenuator (BTLA) on CD8+ TIL. Interestingly, assessment of mutation load (ML) of the tumors prior to TIL ACT showed that the check point naïve group display a high ML ( > 100) within their tumor whereas some patients who had Ipi prior to TIL have a low ML ( < 100). Conclusions: Our preliminary analysis shows that pre-treatment with Ipi decreases ORR to TIL ACT. Understanding how prior ipi modifies TIL, the tumor and microenvironment will help to define the full extent of the impact and how to best treat Ipi refractory pts with TIL. Clinical trial information: NCT00338377.

scholarly journals Adoptive Cell Therapy with Tumor Infiltrating Lymphocytes and Intermediate Dose Interleukin-2 for Metastatic Melanoma

2014 ◽  
Vol 25 ◽  
pp. iv361
Author(s):  
R. Andersen ◽  
M. Donia ◽  
E. Ellebaek Steensgaard ◽  
T. Holz Borch ◽  
T. Zeeberg Iversen ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Metastatic Melanoma ◽  
Adoptive Cell Therapy ◽  
Interleukin 2 ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes ◽  
Intermediate Dose

scholarly journals Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma

2018 ◽  
Vol 8 ◽  
Author(s):  
John E. Mullinax ◽  
MacLean Hall ◽  
Sangeetha Prabhakaran ◽  
Jeffrey Weber ◽  
Nikhil Khushalani ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Metastatic Melanoma ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

scholarly journals Cell therapies in ovarian cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110083
Author(s):  
Apostolos Sarivalasis ◽  
Matteo Morotti ◽  
Arthur Mulvey ◽  
Martina Imbimbo ◽  
George Coukos
Keyword(s):  
Ovarian Cancer ◽  
T Cell ◽  
Cell Therapy ◽  
Ex Vivo ◽  
Gynecological Cancer ◽  
Adoptive Cell Therapy ◽  
Survival Rates ◽  
Tumor Infiltrating Lymphocytes ◽  
T Cell Therapy ◽  
Cell Therapies

Epithelial ovarian cancer (EOC) is the most important cause of gynecological cancer-related mortality. Despite improvements in medical therapies, particularly with the incorporation of drugs targeting homologous recombination deficiency, EOC survival rates remain low. Adoptive cell therapy (ACT) is a personalized form of immunotherapy in which autologous lymphocytes are expanded, manipulated ex vivo, and re-infused into patients to mediate cancer rejection. This highly promising novel approach with curative potential encompasses multiple strategies, including the adoptive transfer of tumor-infiltrating lymphocytes, natural killer cells, or engineered immune components such as chimeric antigen receptor (CAR) constructs and engineered T-cell receptors. Technical advances in genomics and immuno-engineering have made possible neoantigen-based ACT strategies, as well as CAR-T cells with increased cell persistence and intratumoral trafficking, which have the potential to broaden the opportunity for patients with EOC. Furthermore, dendritic cell-based immunotherapies have been tested in patients with EOC with modest but encouraging results, while the combination of DC-based vaccination as a priming modality for other cancer therapies has shown encouraging results. In this manuscript, we provide a clinically oriented historical overview of various forms of cell therapies for the treatment of EOC, with an emphasis on T-cell therapy.

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