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Unlocking the Promise of Vaccines for Cancer Treatment

Jaime Rosenberg
This is part 3 of a 3-part vaccine series covering the potential of vaccines for infectious diseases, the impact of the antivaccination movement, and the promise of vaccines for cancer treatment. Read part 1 and part 2

The vaccine targets the GUCY2C molecule, which is present in intestinal epithelial cells. According to Snook, when these cells are infected by colon cancer, they keep expressing the molecule, and when the cancer spreads to other places in the body, the molecule stays with it. As a result, GUCY2C has been identified as an important biomarker in the disease. The researchers combined the GUCY2C molecule with a molecule that boosts immune response and loaded it into an adenovirus vector.

The benefit of having the vaccine is its potential for efficacy long term, said Snook. While chemotherapy stops working once therapy is completed, vaccines can induce an immune response that lasts for years or decades. In addition to sustained efficacy, vaccines also offer fewer side effects than chemotherapy, which is often used following tumor resection to prevent recurrence.

The clinical trial enrolled 10 patients with stage 1 or stage 2 colon cancer who received 1 dose and then came back for blood draws at 30, 90, and 180 days following vaccination. During the study period, patients experienced discomfort at the site of injection, but there were no serious side effects reported. The researchers also observed that the vaccine was able to elicit an immune response and activate killer T-cells in about half the patients.

Since starting the trial, the researchers found that other intestinal cancers express the GUCY2C molecule, including gastric, esophageal, and pancreatic cancer. Moving forward, the researchers have modified the vaccine to try and improve response rates and are preparing for a phase 2 trial that will include the modified vaccine and patients with the 4 different types of cancer.

For Ezra Cohen, MD, FRCPSC, FASCO, medical oncologist and associate director of Translational Science at Moores Cancer Center, and professor of medicine at University of California San Diego Health, previous and current vaccines have failed because they've largely ignored the biology, often searching for common tumor antigens that are likely irrelevant to the biology of a patient’s cancer and immune response, he explained in an interview with AJMC®.

Cohen and researchers from the University of California San Diego Health and La Jolla Institute for Allergy and Immunology are working on a vaccine in the metastatic setting that’s specific to each patient’s cancer.

“About 4 years ago, we began thinking: we know every cancer is different at a molecular level, and we know everyone’s immune system responds differently to different antigens, and given these 2 facts, designing therapies that are ignoring that biology are never going to get us to where we want to be, which, boldly, is curing metastatic disease,” said Cohen.

Once the neoantigens in a patient’s cancer are identified, the researchers then identify peptides that can be utilized to create a vaccine to stimulate an immune response. The vaccination is used in combination with pembrolizumab (Keytruda) to boost initial immune response.

The phase 1b study is currently enrolling 10 patients to test the personalized vaccine. The first patient enrolled in the study, who has stage 4 pancreatic neuroendocrine cancer, has had stable disease since September when she began receiving the 3 doses of the vaccine each 3 weeks apart. According to Cohen, a biopsy showed that the mutations she was immunized against from the vaccine were gone. The 1 remaining mutation that the researchers could not create the peptide for was still there, almost serving as a positive control, he explained.

Along the way, the researchers have learned how to tweak the vaccine to potentially make it more effective. In a preclinical model, they noticed that by initially clustering the vaccine and giving 3 doses each a week apart and then administering 3 more doses each 3 weeks apart, there was a better immune response.

Reference
Cheever M, Higano C. PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine [published online June 2011]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-10-3126.
 

 
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