P10s-PADRE vaccine combined with neoadjuvant chemotherapy in ER-positive breast cancer patients induces humoral and cellular immune responses
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Issam Makhoul1,6, Saddam Mohammed Ibrahim2,7, Muhammad Abu-Rmaileh4, Fariba Jousheghany2, Eric R. Siegel3, Lora J. Rogers1, John J. Lee2, Sergio Pina-Oviedo2, Ginell R. Post2, J. Thaddeus Beck5, Thomas Kieber-Emmons2 and Behjatolah Monzavi-Karbassi2,6
1 Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
2 Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
3 Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
4 Department of Internal Medicine, University of Texas Southwestern, Dallas, TX 75390, USA
5 Highland Oncology Group, Fayetteville, AR 72703, USA
6 Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
7 UnivLyon, Université Claude Bernard Lyon 1, Villeurbanne 69100, France
|Behjatolah Monzavi-Karbassi,||email:||[email protected]|
Keywords: cancer vaccine; peptide mimotopes; combination therapy; breast cancer
Received: August 24, 2021 Accepted: September 11, 2021 Published: October 26, 2021
Breast cancer patients diagnosed with HR+/HER2– tumors face a persistent risk of distant recurrence long after completion of their treatment. Strategies to induce anti-tumor immune responses could complement standard-of-care therapies for these patients. The current study was performed to examine the feasibility, safety and immunogenicity of adding P10s-PADRE to standard-of-care chemotherapy in HR+/HER2− early-stage breast cancer patients. Twenty-five subjects were treated in a single-arm Phase Ib clinical trial. Five different immunization schedules were considered to evaluate the feasibility of eliciting an immune response. The primary immunogenicity endpoint was antibody titer. The expression of several activation markers on natural killer (NK) cells and serum concentrations of Th1/Th2 cytokines were also examined. The percentage of tumor-infiltrating lymphocytes (TILs) was determined. Antibody response was superior in schedule C where 3 weekly immunizations preceded the first dose of chemotherapy. A significant change in CD16, NKp46 and CD94 expression levels on NK cells and a rise in serum content of IFN-γ was observed after treatment. Schedule C showed an increase in TILs in residual lesions. The combination therapy is safe and immunogenic with treatment schedule C being immunologically promising. Randomized trials focused on long-term survival outcomes are needed to evaluate clinical benefits.
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