Single-cell analysis of oncolytic virotherapy in adult T-cell leukemia/lymphoma.

in Journal for immunotherapy of cancer by Jianhong An, Erqiang Hu, Yang Shi, Yanan Fang, Naijia Liu, Qiang Liu, Qing Wang, Yanhua Wang, Wu He, Angelina Wang, Yinghui Song, Jidong Shan, Jinghang Zhang, Yiyu Zou, Haiying Cheng, Rafi Kabarriti, Wei Cai, Amit Verma, Roberto Alejandro Sica, Wenjun Deng, Shanye Yin

TLDR

  • This case report presents the first reported use of talimogene laherparepvec (T-VEC) in treating adult T-cell leukemia/lymphoma, resulting in substantial tumor regression and clinical stabilization.

Abstract

Adult T-cell leukemia/lymphoma (ATLL), an aggressive T-cell malignancy associated with human T-cell leukemia virus type 1, presents significant therapeutic challenges due to high relapse rates and resistance to therapy. Here, we present the first reported case of ATLL treated with talimogene laherparepvec (T-VEC), an oncolytic viral immunotherapy approved for unresectable melanoma. The patient, who had experienced disease progression despite multiple lines of chemotherapy, radiotherapy, immunotherapy, and targeted therapy, underwent experimental virotherapy with two intratumoral T-VEC injections. The treatment was well-tolerated, with no significant adverse effects, and led to substantial tumor regression and clinical stabilization, suggesting potential remission. Single-cell analysis revealed that T-VEC treatment induced robust local and systemic immune responses, including tumor necrosis, activation of M1 macrophages, and infiltration of CD8+ effector memory T cells. These findings demonstrate T-VEC's safety and efficacy in generating both localized oncolysis and systemic anti-tumor immune response, highlighting its promise as a novel therapeutic approach for refractory ATLL.

Overview

  • The study presents the first reported case of adult T-cell leukemia/lymphoma (ATLL) treated with talimogene laherparepvec (T-VEC), an oncolytic viral immunotherapy.
  • The patient had experienced disease progression despite multiple lines of chemotherapy, radiotherapy, immunotherapy, and targeted therapy.
  • The study aimed to test the safety and efficacy of T-VEC in generating both localized oncolysis and systemic anti-tumor immune response in refractory ATLL.

Comparative Analysis & Findings

  • T-VEC treatment led to substantial tumor regression and clinical stabilization, suggesting potential remission.
  • Single-cell analysis revealed robust local and systemic immune responses, including tumor necrosis, activation of M1 macrophages, and infiltration of CD8+ effector memory T cells.
  • The treatment was well-tolerated, with no significant adverse effects.

Implications and Future Directions

  • The study highlights the promise of T-VEC as a novel therapeutic approach for refractory ATLL, providing a potential new treatment option for patients with this aggressive T-cell malignancy.
  • Future studies could investigate the optimal dosing and administration schedule of T-VEC for ATLL, as well as its combination with other therapies to enhance anti-tumor activity.
  • Understanding the mechanisms underlying T-VEC-induced immune responses and tumor regression could inform the development of new immunotherapies for ATLL and other cancers.