Tag: cancer vaccine

Company News: ISA Pharmaceuticals – New Study Explains Synergy between Cancer Vaccine ISA101 and Chemotherapy

Tumor necrosis factor alpha (TNFα) produced by T cells following vaccination sensitizes tumor cells for eradication by certain chemotherapeutics

Data published in Clinical Cancer Research support ongoing clinical development of ISA101

ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, has announced new findings on the synergy between its synthetic long peptide (SLP®) cancer vaccine and chemotherapeutics. Data published in Clinical Cancer Research* demonstrate that combined chemo-immunotherapy leads to superior T cell-mediated tumor eradication in the absence of T cell immunosuppression.

In a preclinical model of cancer induced by human papillomavirus type 16 (HPV16), ISA’s lead SLP® candidate ISA101 was combined with seven clinically relevant chemotherapeutics to treat established tumors. The researchers tested either ISA101 or chemotherapeutics alone as well as combinations of both. Topotecan, gemcitabine, carboplatin and cisplatin showed synergies with ISA101. The most effective combination was cisplatin plus ISA101, resulting in tumor regression and the durable survival of 75% of the mice, and a lasting immune response. Most importantly, synergy occurred to the same extent at only 40% of the maximum tolerated dose (MTD) of cisplatin, allowing for a reduction of chemotherapy-associated side effects as seen at MTD. There was no synergy between ISA101 and oxaliplatin, doxorubicin or paclitaxel.

While synergy was not related to overt changes in systemic T cell immunity or increased sensitivity of cisplatin-treated TC-1 tumor cells towards CTL-mediated killing, there was a strongly enhanced leukocyte infiltration of the tumor. Vaccine-specific polyfunctional CD8 T cells were a major component of this infiltration. The cisplatin allowed these cells to migrate earlier into the tumor beds, enabling them to eliminate tumor cells at an earlier stage of disease. Once inside the tumor, the T cells further enhanced tumor cell death by producing pro-inflammatory cytokines such as IFNγ and TNFα. In particular, TNFα produced by intratumoral T cells sensitized the tumor cells for cisplatin, allowing for synergistic cell death.

Another study presented at AACR in 2014, showed that cis-/carboplatin/paclitaxel depletes myeloid derived suppressor cells in patients, and thereby strongly increases an ISA101-mediated immune response.

This finding supports the ongoing clinical development program in which ISA101 is tested in a Phase I/II study (CervISA) in combination with cisplatin/carboplatin and paclitaxel in women with advanced or recurrent cervical cancer.

 

* van der Sluis TC et al.: Vaccine-induced Tumor Necrosis Factor producing T-cells synergize with cisplatin to promote tumor cell death. Clin Cancer Res. 2014 Dec. 12 pii: clincanres.2142.2014; Epub 2014 Dec. 12,; doi: 10.1158/1078-0432.CCR-14-2142

Company News: New Clinical Data Demonstrate Strong Synergy between Cancer Vaccine ISA101 and Chemotherapy

–      Data presented at the AACR Annual Meeting 2014

–      Potential new treatment being developed for patients with late-stage cervical cancer

ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed therapeutic vaccines against cancer and persistent viral infections, has announced new clinical data on its lead product candidate ISA101. ISA101 is a therapeutic cancer vaccine for the treatment of high-risk, HPV16-induced diseases, such as cervical cancer. The data were presented by principal investigator Prof. Sjoerd van der Burg, Ph.D., at this year’s American Association for Cancer Research (AACR) Annual Meeting in San Diego.

The data demonstrate strong synergy between ISA101 and chemotherapy, offering potential new treatment options for cervical cancer patients scheduled to receive standard chemotherapy with carboplatin / paclitaxel.

Prof. van der Burg and his group evaluated the immunological and clinical responses of patients with advanced cervical carcinoma in a Phase I combination trial. In this pilot trial, patients received ISA101 in combination with standard chemotherapy cycles (carboplatin / paclitaxel). Almost all patients showed a strong immune response to the ISA101 vaccine. Comprehensive immune monitoring confirmed the beneficial effect of myeloid suppressor cell depletion associated with a robust induction of HPV16-specific T-cell responses that were sustained throughout several cycles of chemotherapy.

The observation that depletion of myeloid suppressor cells by a carboplatin/paclitaxel chemotherapy regimen enhances the immune response to ISA101 is in line with prior observations that tumors promote immune tolerance starting early in the disease and that chemotherapy can restore immune competence in cancer patients.

Based on these results ISA has initiated a phase I/II study (CervISA) in October last year testing ISA101 in combination with carboplatin, paclitaxel and pegylated interferon alpha in women with advanced or recurrent cervical cancer.

The presentation titled “Synergistic effects of properly timed HPV16 SLP vaccination during standard carboplatin-paclitaxel chemotherapy in animals and patients with metastatic cervical carcinoma“ was given at the Minisymposium MS.IM02.01 “Immune-based Therapies: Responses, Biomarkers, and Mechanisms” on Monday, April 07, 2014, at 3:20 PM in Room 6CF at the San Diego Convention Center.

The abstract # 2938 is available at the AACR website www.aacr.org.

Company News: New Clinical Data on Cancer Vaccine ISA101 to Be Presented at the AACR Annual Meeting 2014

ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed therapeutic vaccines against cancer and persistent viral infections, today announced that principal investigator Prof. Sjoerd van der Burg, Ph.D., will present new clinical data on ISA101 at this year’s American Association for Cancer Research (AACR) Annual Meeting. ISA101 is a therapeutic cancer vaccine for the treatment of high-risk, HPV16-induced diseases.

The presentation titled “Synergistic effects of properly timed HPV16 SLP vaccination during standard carboplatin-paclitaxel chemotherapy in animals and patients with metastatic cervical carcinoma“ will be given at the Minisymposium MS.IM02.01 “Immune-based Therapies: Responses, Biomarkers, and Mechanisms” on Monday, April 07, 2014, at 3:20 PM in Room 6CF at the San Diego Convention Center.

The abstract # 2938 is available at the AACR website www.aacr.org.

Company News: ISA Pharmaceuticals Presents Novel Data at the European Cancer Congress 2013 – Strong Synergies Between Cancer Vaccine ISA101 and Chemotherapy

– Chemotherapy improves immune response to therapeutic vaccine against Human Papilloma Virus type 16 (HPV16) –

ISA Pharmaceuticals B.V., a clinical-stage biopharmaceutical company focusing on rationally designed therapeutic vaccines against cancer and persistent viral infections, today announced that it had presented novel data on its lead compound ISA101 at this year´s European Cancer Congress (ECCO-ESMO-ESTRO) in Amsterdam, The Netherlands.

In a preclinical mouse model of cancer, chemotherapy with cisplatin increased the therapeutic response to subsequent vaccination with an HPV16 synthetic long peptide (SLP®). While cisplatin or HPV-SLP® treatment alone increased survival, long-term survival was only achieved by combining chemotherapy with the vaccine.

These findings are further supported by a Phase I toxicity / immunogenicity study in 18 women with advanced or recurrent cervical cancer eligible for chemotherapy. Concurrent with standard chemotherapy (including carboplatin and paclitaxel), 12 patients received ISA101, a therapeutic cancer vaccine consisting of 13 synthetic long peptides from the E6 and E7 oncoproteins of HPV16. The control group (n=6) did not receive vaccination. The study demonstrates that chemotherapy doe s not cause lymphodepletion or suppression of cellular immune responses in patients. Patients showed shifts in leukocyte composition associated with increased dendritic cell function and improved memory T cell responses to common recall antigens. Patients treated with chemotherapy and ISA101 exhibited robust and sustained HPV16-specific proliferative T cell responses.