Miguel Bronchud, Veteran Cancer Clinician and Researcher and Co-Founder of Regenerative Medicine Solutions, shared on LinkedIn:
“A vaccine for Ductal Carcinoma in Situ of the Breast?
An original approach pending phase II and phase III studies (& presumably a long -at least five years follow up of patients – thereafter…)
‘Safety and immunogenicity of a tri-antigen vaccine targeting IGFBP-2, HER2, and IGF-IR in participants with non-metastatic breast cancer’
– recently published by USA colleagues from several institutions
Corresponding author -Mary L Disis, UW Medicine Cancer Vaccine Institute, University of Washington, Seattle, Washington, USA
ndisis@uw.edu.
Ductal carcinoma in situ (DCIS) is a preinvasive form of breast cancer. In this context the vaccine approaches can be considered cancer interception studies, testing what is considered a dream of many – stopping cancer before it is truly cancer?
Current treatment – to eliminate this Pre Cancer breast lesions (not at all uncommon) and to reduce the risk of transformation into an invasive type of cancer, usually clinically consists of surgery, radiation, and often systemic oral endocrine therapy – inevitably exposing patients to unnecessary health risks.
Vaccines targeting DCIS may be a way to intercept preinvasive lesions and prevent the development of invasive breast cancer.
Scientists developed a Th1 selective multiantigen, polyepitope plasmid-DNA vaccine encoding segments of IGFBP-2, HER2, and IGF-IR, all antigens expressed in hormone receptor positive and negative DCIS. Researchers then performed a Phase I study in participants with non-metastatic breast cancer with no evidence of disease.
The primary objective was to assess the safety of 3 monthly intradermal doses (150, 300, or 600 µg) of the tri-antigen vaccine with granulocyte macrophage colony-stimulating factor as an adjuvant. 32 participants were enrolled, 10 per dose level.
Toxicity evaluations occurred monthly with vaccination and at 1 and 6 months after the last vaccine. Blood was collected at baseline and at 1 and 6 months after the last immunization to assess cellular immune responses. Participants were followed annually for 5 years for long-term toxicity.
There was no significant difference in adverse events (AEs) across dose levels and all related AEs were grades 1 or 2. All doses were immunogenic – responders included:
- 70% of participants at the 150 µg dose level,
- 67% at the 300 µg dose,
- 40% at the 600 µg dose level.
All participants at the 300 µg dose retained significant Th1-antigen-specific immune response at 6 months after end of immunizations.
T-cells derived from vaccine immunologic responders exhibited gene expression profiles that indicated an increased metabolic fitness as compared with immunologic non-responders.
The tri-antigen vaccine appears safe and immunogenic. The intermediate dose (300 µg) was chosen as the Phase II dose due to the long-term persistence of immunity after vaccination. The vaccine will be studied in Phase II trials for the treatment of DCIS.”
Title: Safety and immunogenicity of a tri-antigen vaccine targeting IGFBP-2, HER2, and IGF-IR in participants with non-metastatic breast cancer
Authors: Sasha E. Stanton, Denise L. Cecil, Howard H. Bailey, Ying Liu, William R. Gwin, Andrew L. Colveler, John B. Liao, Kari B. Wisinski, Lisa Barroilhet, KyungMann Kim, Thomas C. Havighurst, Katina DeShong, Kyleigh Twaroski, Jennifer S. Childs, Eileen Dimond, Margaret Wojtowicz, Brandy M. Heckman-Stoddard, Mary L. Disis
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