scholarly journals Minimally Cultured Tumor-infiltrating Lymphocytes Display Optimal Characteristics for Adoptive Cell Therapy

2008 ◽  
Vol 31 (8) ◽  
pp. 742-751 ◽  
Author(s):  
Khoi Q. Tran ◽  
Juhua Zhou ◽  
Katherine H. Durflinger ◽  
Michelle M. Langhan ◽  
Thomas E. Shelton ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

scholarly journals 353 Safety and efficacy of tumor infiltrating lymphocytes (TIL, LN-145) in combination with pembrolizumab for advanced, recurrent or metastatic HNSCC

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A378-A378
Author(s):  
Antonio Jimeno ◽  
Sophie Papa ◽  
Missak Haigentz ◽  
Juan Rodríguez-Moreno ◽  
Julian Schardt ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Checkpoint Inhibitors ◽  
Adoptive Cell Therapy ◽  
Single Agent ◽  
Objective Response ◽  
Tumor Resection ◽  
Tumor Infiltrating Lymphocytes ◽  
Open Label ◽  
Safety And Efficacy ◽  
Infiltrating Lymphocytes

BackgroundSingle agent checkpoint inhibitors (CPI) are an approved first or second-line therapy in head and neck squamous cell carcinoma (HNSCC), but their efficacy is limited. Adoptive cell therapy with tumor infiltrating lymphocytes (TIL, LN-145) has demonstrated efficacy in multiple malignancies alone or in combination with CPI. To improve HNSCC therapy, a combination of pembrolizumab and LN-145 was explored.MethodsIOV-COM-202 is an ongoing Phase 2 multicenter, multi-cohort, open-label study evaluating LN-145 in multiple settings and indications, and here we report cohort 2A which enrolled CPI naïve HNSCC patients who received the combination of LN-145 and pembrolizumab. Key eligibility criteria include up to 3 lines of prior therapy, ECOG <1, at least one resectable metastasis for LN-145 production, and at least another measurable lesion after tumor resection. Primary endpoints are ORR per RECIST v1.1 by investigator and safety as measured by the incidence of grade ≥ 3 treatment-emergent adverse events (TEAEs). LN-145 production method uses central GMP manufacturing in a 22-day process yielding a cryopreserved TIL product (figure 1). Preconditioning chemotherapy consists of cyclophosphamide/fludarabine, followed by LN-145, and then < 6 doses of IL-2 over <3 days. Pembrolizumab is initiated post-tumor harvest but prior to LN-145 and continues after LN-145 infusion Q3W until toxicity or progression (figure 2).ResultsNine (N=9) HNSCC patients have received LN-145 plus pembrolizumab, with a median duration of follow up of 6.9 months. Nine and 8 patients were evaluable for safety and efficacy, respectively. Mean number of prior therapies was 1.1 with 89% of the patients having received prior chemotherapy. Four were HPV+, 2 HPV-, 3 unknown. The Treatment Emergent Adverse Event (TEAE) profile was consistent with the underlying advanced disease and the known AE profiles of pembrolizumab, the lymphodepletion and IL-2 regimens. The most common TEAE were chills, hypotension, anemia, thrombocytopenia, pyrexia, fatigue and tachycardia. Four patients had a confirmed, objective response with an ORR of 44% (1 CR, 3 PR, 4 SD, 1 NE) per RECIST 1.1. The disease control rate at data cutoff was 89% in 9 patients, and 7 of the 8 evaluable patients (87.5%) had a reduction in target lesions. Median DOR was not reached.Abstract 353 Figure 1Iovance LN-145 (autologous TIL cell therapy product) ManufacturingAbstract 353 Figure 2IOV-COM-202 Study SchemaConclusionsLN-145 can be safely combined with pembrolizumab in patients with metastatic HNSCC. LN-145 plus pembrolizumab shows early signs of improved efficacy particularly when compared with literature reports of pembrolizumab alone in a comparable patient population. Enrollment is ongoing and updated data will be presented.Trial RegistrationNCT03645928Ethics ApprovalThe study was approved by Advarra Institutional Review Board, under protocol number: Pro00035064.

Cytologic Evaluation of Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy

2020 ◽  
Vol 153 (4) ◽  
pp. 513-523
Author(s):  
Sara E Monaco ◽  
Liron Pantanowitz ◽  
Juan Xing ◽  
Jackie Cuda ◽  
Udai S Kammula
Keyword(s):  
Clinical Trial ◽  
Cell Therapy ◽  
Metastatic Cancer ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Lymphoid Cells ◽  
Cytotoxic T Cell ◽  
Cell Therapies ◽  
Clinicopathologic Findings ◽  
Infiltrating Lymphocytes

Abstract Objectives Novel immunotherapeutic options for refractory metastatic cancer patients include adoptive cell therapies such as tumor infiltrating lymphocytes (TILs). This study characterizes the clinicopathologic findings in a cohort of TIL specimens. Methods Patients with metastatic malignancy who were eligible had TILs from their metastases grown and expanded and then sent to pathology. Results A total of 11 TIL specimens (10 melanoma, 1 adenocarcinoma) from patients enrolled in an experimental clinical trial were reviewed. All specimens showed more than 200 lymphoid cells, stained positive for lymphoid markers confirming an activated cytotoxic T-cell immunophenotype, and morphologically showed an intermediate-sized population with immature chromatin and frequent mitoses. Six cases (55%) showed large cells with nucleomegaly and prominent nucleoli. Conclusions This report is the first describing cytopathologic findings of autologous TIL therapy including adequacy guidelines and expected cytomorphologic and immunophenotypic findings. To meet this novel clinical demand, a predefined cytology protocol to rapidly process and interpret these specimens needs to be established.

scholarly journals Adoptive cell therapy with tumor-infiltrating lymphocytes in patients with metastatic ovarian cancer: a pilot study

2018 ◽  
Vol 7 (12) ◽  
pp. e1502905 ◽  
Author(s):  
Magnus Pedersen ◽  
Marie Christine Wulff Westergaard ◽  
Katy Milne ◽  
Morten Nielsen ◽  
Troels Holz Borch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Pilot Study ◽  
Cell Therapy ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

Cardiovascular Toxicity and Mortality Associated With Adoptive Cell Therapy and Tumor-infiltrating Lymphocytes for Advanced Stage Melanoma

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Michael G. Fradley ◽  
Rongras Damrongwatanasuk ◽  
Sanjay Chandrasekhar ◽  
Mohammed Alomar ◽  
Kevin E. Kip ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Advanced Stage ◽  
Cardiovascular Toxicity ◽  
Infiltrating Lymphocytes

scholarly journals Adoptive cell therapy with tumor-infiltrating lymphocytes for patients with metastatic ovarian cancer: A pilot study

2017 ◽  
Vol 28 ◽  
pp. v407 ◽  
Author(s):  
M. Pedersen ◽  
M. Westergaard ◽  
M. Nielsen ◽  
T.H. Borch ◽  
L.G. Poulsen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Pilot Study ◽  
Cell Therapy ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

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 Tumor-infiltrating lymphocytes from human prostate tumors reveal anti-tumor reactivity and potential for adoptive cell therapy

2019 ◽  
Vol 8 (12) ◽  
pp. e1672494 ◽  
Author(s):  
Sharon Yunger ◽  
Assaf Bar El ◽  
Li-at Zeltzer ◽  
Eddie Fridman ◽  
Gil Raviv ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Human Prostate ◽  
Prostate Tumors ◽  
Infiltrating Lymphocytes
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