Using Adoptive Cell Therapy in the Modern Era of Metastatic Melanoma Treatment

2017 ◽  
Vol 2 (1-2) ◽  
pp. 32-38
Author(s):  
Meredith McKean ◽  
Rodabe Amaria
Keyword(s):  
Cell Therapy ◽  
Metastatic Melanoma ◽  
Adoptive Cell Therapy ◽  
Melanoma Treatment ◽  
Modern Era

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.

Adoptive Cell Therapy for metastatic melanoma: A UK centre experience.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 9060-9060
Author(s):  
Manon Rhys Pillai ◽  
Ryan Guest ◽  
Natalia Kirillova ◽  
Shien Chow ◽  
Paul Lorigan ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Metastatic Melanoma ◽  
Adoptive Cell Therapy

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.

Abstract CT226: A pilot study of adoptive cell therapy with in vitro educated MART1 T cells in combination with ipilimumab for the treatment of metastatic melanoma

2015 ◽  
Author(s):  
leila Khoja ◽  
Anthony M. Joshua ◽  
Lisa Wang ◽  
David Hogg ◽  
Linh Nguyen ◽  
...  
Keyword(s):  
T Cells ◽  
Pilot Study ◽  
Cell Therapy ◽  
Metastatic Melanoma ◽  
Adoptive Cell Therapy

scholarly journals Minimally invasive liver resection to obtain tumor-infiltrating lymphocytes for adoptive cell therapy in patients with metastatic melanoma

2012 ◽  
Vol 10 (1) ◽  
pp. 113 ◽  
Author(s):  
Melissa M Alvarez-Downing ◽  
Suzanne M Inchauste ◽  
Mark E Dudley ◽  
Donald E White ◽  
John R Wunderlich ◽  
...  
Keyword(s):  
Liver Resection ◽  
Cell Therapy ◽  
Minimally Invasive ◽  
Metastatic Melanoma ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Minimally Invasive Liver Resection ◽  
Infiltrating Lymphocytes

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

Adoptive cell therapy for metastatic melanoma patients: clinical and pre-clinical development

2006 ◽  
Vol 16 (Supplement 1) ◽  
pp. S42
Author(s):  
J. Schachter ◽  
A. Treves ◽  
R. Shapira-Frommer ◽  
D. Barak ◽  
O. Itzhaki ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Metastatic Melanoma ◽  
Adoptive Cell Therapy ◽  
Clinical Development ◽  
Melanoma Patients

scholarly journals Adoptive cell therapy for the treatment of patients with metastatic melanoma

2009 ◽  
Vol 21 (2) ◽  
pp. 233-240 ◽  
Author(s):  
Steven A Rosenberg ◽  
Mark E Dudley
Keyword(s):  
Cell Therapy ◽  
Metastatic Melanoma ◽  
Adoptive Cell Therapy

CT halo sign as an imaging marker for response to adoptive cell therapy in metastatic melanoma with pulmonary metastases

2014 ◽  
Vol 24 (6) ◽  
pp. 1251-1256 ◽  
Author(s):  
Shai Shrot ◽  
Jacob Schachter ◽  
Ronnie Shapira-Frommer ◽  
Michal J. Besser ◽  
Sara Apter
Keyword(s):  
Cell Therapy ◽  
Metastatic Melanoma ◽  
Pulmonary Metastases ◽  
Adoptive Cell Therapy ◽  
Halo Sign
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