Supplementary Figure 3 from Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Pesonen, Sari; Diaconu, Iulia; Kangasniemi, Lotta; Ranki, Tuuli; Kanerva, Anna; Pesonen, Saila K.; Gerdemann, Ulrike; Leen, Ann M.; Kairemo, Kalevi; Oksanen, Minna; Haavisto, Elina; Holm, Sirkka-Liisa; Karioja-Kallio, Aila; Kauppinen, Satu; Partanen, Kaarina P. L.; Laasonen, Leena; Joensuu, Tima; Alanko, Tuomo; Cerullo, Vincenzo; Hemminki, Akseli

doi:10.1158/0008-5472.22392483.v1

Supplementary Figure 3 from Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

journal contribution

posted on 2023-03-30, 21:07 authored by Sari Pesonen, Iulia Diaconu, Lotta Kangasniemi, Tuuli Ranki, Anna Kanerva, Saila K. Pesonen, Ulrike Gerdemann, Ann M. Leen, Kalevi Kairemo, Minna Oksanen, Elina Haavisto, Sirkka-Liisa Holm, Aila Karioja-Kallio, Satu Kauppinen, Kaarina P. L. Partanen, Leena Laasonen, Tima Joensuu, Tuomo Alanko, Vincenzo Cerullo, Akseli Hemminki

PDF file - 1.1MB, (A) Patient serum samples were analyzed for Th1 induced cytokines interferon-� (IFN-�), tumor necrosis factor-� (TNF-�) and interleukin-2 (IL-2) and Th2 cytokines interleukin-4 (IL-4), interleukin-5 (IL-5) and Interleukin 10 (IL-10). The ratio between Th1 and Th2 type cytokines was assessed. Cytokines levels are reported relative to their baseline level, which was set as 1 and a ratio between Th1/Th2 was calculated for each time point. (B) Malignant ascites of patient R8 and pleural effusion of patient T181 were analyzed for Th1 induced cytokines IFN-� and IL-2, and for Th2 induced IL-10 before and after treatment.

History

ARTICLE ABSTRACT

The immunosuppressive environment of advanced tumors is a primary obstacle to the efficacy of immunostimulatory and vaccine approaches. Here, we report an approach to arm an oncolytic virus with CD40 ligand (CD40L) to stimulate beneficial immunologic responses in patients. A double-targeted chimeric adenovirus controlled by the hTERT promoter and expressing CD40L (CGTG-401) was constructed and nine patients with progressing advanced solid tumors refractory to standard therapies were treated intratumorally. No serious adverse events resulting in patient hospitalization occurred. Moderate or no increases in neutralizing antibodies were seen, suggesting effective Th1 immunologic effects. An assessment of the blood levels of virus indicated 17.5% of the samples (n = 40) were positive at a low level early after treatment, but not thereafter. In contrast, high levels of virus, CD40L, and RANTES were documented locally at the tumor. Peripheral blood mononuclear cells were analyzed by IFN-γ ELISPOT analysis and induction of both survivin-specific and adenovirus-specific T cells was seen. Antitumor T-cell responses were even more pronounced when assessed by intracellular cytokine staining after stimulation with tumor type–specific peptide pools. Of the evaluable patients, 83% displayed disease control at 3 months and in both cases in which treatment was continued the effect was sustained for at least 8 months. Injected and noninjected lesions responded identically. Together, these findings support further clinical evaluation of CGTG-401. Cancer Res; 72(7); 1621–31. ©2012 AACR.