Dataset Information

First in man study: Bcl-Xl_42-CAF^®09b vaccines in patients with locally advanced prostate cancer.

ABSTRACT:

Background

The B-cell lymphoma-extra-large (Bcl-XL) protein plays an important role in cancer cells' resistance to apoptosis. Pre-clinical studies have shown that vaccination with Bcl-XL-derived peptides can induce tumor-specific T cell responses that may lead to the elimination of cancer cells. Furthermore, pre-clinical studies of the novel adjuvant CAF^®09b have shown that intraperitoneal (IP) injections of this adjuvant can improve the activation of the immune system. In this study, patients with hormone-sensitive prostate cancer (PC) received a vaccine consisting of Bcl-XL-peptide with CAF^®09b as an adjuvant. The primary aim was to evaluate the tolerability and safety of IP and intramuscular (IM) administration, determine the optimal route of administration, and characterize vaccine immunogenicity.

Patients and methods

Twenty patients were included. A total of six vaccinations were scheduled: in Group A (IM to IP injections), ten patients received three vaccines IM biweekly; after a three-week pause, patients then received three vaccines IP biweekly. In Group B (IP to IM injections), ten patients received IP vaccines first, followed by IM under a similar vaccination schedule. Safety was assessed by logging and evaluating adverse events (AE) according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.0). Vaccines-induced immune responses were analyzed by Enzyme-Linked Immunospot and flow cytometry.

Results

No serious AEs were reported. Although an increase in T cell response against the Bcl-XL-peptide was found in all patients, a larger proportion of patients in group B demonstrated earlier and stronger immune responses to the vaccine compared to patients in group A. Further, we demonstrated vaccine-induced immunity towards patient-specific CD4, and CD8 T cell epitopes embedded in Bcl-XL-peptide and an increase in CD4 and CD8 T cell activation markers CD107a and CD137 following vaccination. At a median follow-up of 21 months, no patients had experienced clinically significant disease progression.

Conclusion

The Bcl-XL-peptide-CAF^®09b vaccination was feasible and safe in patients with l hormone-sensitive PC. In addition, the vaccine was immunogenic and able to elicit CD4 and CD8 T cell responses with initial IP administration eliciting early and high levels of vaccine-specific responses in a higher number og patients.

Clinical trial registration

https://clinicaltrials.gov, identifier NCT03412786.

SUBMITTER: Mork SK

PROVIDER: S-EPMC10043415 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

First in man study: Bcl-Xl_42-CAF<sup>®</sup>09b vaccines in patients with locally advanced prostate cancer.

Mørk Sofie Kirial SK Kongsted Per P Westergaard Marie Christine Wulff MCW Albieri Benedetta B Granhøj Joachim Stoltenborg JS Donia Marco M Martinenaite Evelina E Holmström Morten Orebo MO Madsen Kasper K Kverneland Anders H AH Kjeldsen Julie Westerlin JW Holmstroem Rikke Boedker RB Lorentzen Cathrine Lund CL Nørgaard Nis N Andreasen Lars Vibe LV Wood Grith Krøyer GK Christensen Dennis D Klausen Michael Schantz MS Hadrup Sine Reker SR Thor Straten Per P Andersen Mads Hald MH Svane Inge Marie IM

Frontiers in immunology 20230314

<h4>Background</h4>The B-cell lymphoma-extra-large (Bcl-XL) protein plays an important role in cancer cells' resistance to apoptosis. Pre-clinical studies have shown that vaccination with Bcl-XL-derived peptides can induce tumor-specific T cell responses that may lead to the elimination of cancer cells. Furthermore, pre-clinical studies of the novel adjuvant CAF<sup>®</sup>09b have shown that intraperitoneal (IP) injections of this adjuvant can improve the activation of the immune system. In thi ...[more]

PMID: 36999039

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Dataset Information

First in man study: Bcl-Xl_42-CAF^®09b vaccines in patients with locally advanced prostate cancer.

Background

Patients and methods

Results

Conclusion

Clinical trial registration

Publications

First in man study: Bcl-Xl_42-CAF<sup>®</sup>09b vaccines in patients with locally advanced prostate cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

First in man study: Bcl-Xl_42-CAF®09b vaccines in patients with locally advanced prostate cancer.

Background

Patients and methods

Results

Conclusion

Clinical trial registration

Publications

First in man study: Bcl-Xl_42-CAF<sup>®</sup>09b vaccines in patients with locally advanced prostate cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

First in man study: Bcl-Xl_42-CAF^®09b vaccines in patients with locally advanced prostate cancer.