Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers

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Santos , J , Heiniö , C , Quixabeira , D , Zafar , S , Clubb , J , Pakola , S , Cervera-Carrascon , V , Havunen , R , Kanerva , A & Hemminki , A 2021 , ' Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers ' , Cells , vol. 10 , no. 5 , 978 .

Title: Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers
Author: Santos, Joao; Heiniö, Camilla; Quixabeira, Dafne; Zafar, Sadia; Clubb, James; Pakola, Santeri; Cervera-Carrascon, Victor; Havunen, Riikka; Kanerva, Anna; Hemminki, Akseli
Contributor organization: Department of Pathology
Faculty of Medicine
TRIMM - Translational Immunology Research Program
University of Helsinki
Research Programs Unit
HUS Comprehensive Cancer Center
HUS Gynecology and Obstetrics
Akseli Eetu Hemminki / Principal Investigator
Department of Obstetrics and Gynecology
Department of Oncology
Date: 2021-05
Language: eng
Number of pages: 14
Belongs to series: Cells
ISSN: 2073-4409
Abstract: Immunotherapy with tumor-infiltrating lymphocytes (TIL) or oncolytic adenoviruses, have shown promising results in cancer treatment, when used as separate therapies. When used in combination, the antitumor effect is synergistically potentiated due oncolytic adenovirus infection and its immune stimulating effects on T cells. Indeed, studies in hamsters have shown a 100% complete response rate when animals were treated with oncolytic adenovirus coding for TNFa and IL-2 (Ad5/3-E2F-D24-hTNFa-IRES-hIL2; TILT-123) and TIL therapy. In humans, one caveat with oncolytic virus therapy is that intratumoral injection has been traditionally preferred over systemic administration, for achieving sufficient virus concentrations in tumors, especially when neutralizing antibodies emerge. We have previously shown that 5/3 chimeric oncolytic adenovirus can bind to human lymphocytes for avoidance of neutralization. In this study, we hypothesized that incubation of oncolytic adenovirus (TILT-123) with TILs prior to systemic injection would allow delivery of virus to tumors. This approach would deliver both components in one self-amplifying product. TILs would help deliver TILT-123, whose replication will recruit more TILs and increase their cytotoxicity. In vitro, TILT-123 was seen binding efficiently to lymphocytes, supporting the idea of dual administration. We show in vivo in different models that virus could be delivered to tumors with TILs as carriers.
Subject: tumor-infiltrating lymphocytes
oncolytic virus
systemic delivery
cell carrier
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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