Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients.

Abstract

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.

• Authors: Michal J Besser, Ronnie Shapira-Frommer, Avraham J Treves, Dov Zippel, Orit Itzhaki, Ester Schallmach, Adva Kubi, Bruria Shalmon, Izhar Hardan, Raphael Catane, Eran Segal, Gal Markel, Sara Apter, Alon Ben Nun, Iryna Kuchuk, Avichai Shimoni, Arnon Nagler, Jacob Schachter
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 32 Issue 4 Pg. 415-23 (May 2009) ISSN: 1537-4513 [Electronic] United States
• PMID: 19342963 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antifungal Agents
• Antineoplastic Agents, Alkylating
• Antiviral Agents
• Interleukin-2
• Granulocyte Colony-Stimulating Factor
• Interferon-gamma
• Cyclophosphamide
• Fluconazole
• Vidarabine
• fludarabine
• Acyclovir

Topics

• Acyclovir (therapeutic use)
• Adult
• Aged
• Antifungal Agents (therapeutic use)
• Antineoplastic Agents, Alkylating (administration & dosage, therapeutic use)
• Antiviral Agents (therapeutic use)
• Cyclophosphamide (administration & dosage, therapeutic use)
• Cytotoxicity, Immunologic (immunology)
• Female
• Fluconazole (therapeutic use)
• Granulocyte Colony-Stimulating Factor (administration & dosage, therapeutic use)
• Humans
• Immunotherapy, Adoptive
• Interferon-gamma (biosynthesis, immunology)
• Interleukin-2 (administration & dosage, immunology, therapeutic use)
• Lymphocyte Activation (immunology)
• Lymphocyte Depletion
• Lymphocytes, Tumor-Infiltrating (immunology, transplantation)
• Male
• Melanoma (drug therapy, immunology, therapy)
• Middle Aged
• Skin Neoplasms (drug therapy, immunology, therapy)
• Vidarabine (administration & dosage, analogs & derivatives, therapeutic use)