Modified polio vaccine improves survival in glioblastoma
20% of patients with malignant brain cancer who received a polio vaccine-based immunotherapy were alive after three years compared to 4% undergoing standard treatment.1 The Phase 1 dose-finding and toxicity trial enrolled 61 subjects with advanced disease.
The vaccine consists of a recombinant nonpathogenic polio-rhinovirus chimera, which recognizes the poliovirus receptor CD155 overexpressed in many solid tumors. It is designed to provoke an immune response after injection into the tumor microenvironment.
“Similar to many immunotherapies, it appears that some patients don’t respond for one reason or another, but if they respond, they often become long-term survivors,” lead author Annick Desjardins of Duke University said.
1. Desjardins A, Gromeier M, Herndon JE nd, Beaubier N, Bolognesi DP, Friedman AH, Friedman HS, McSherry F, Muscat AM, Nair S, Peters KB, Randazzo D, Sampson JH, Vlahovic G, Harrison WT, McLendon RE, Ashley D, Bigner DD. Recurrent Glioblastoma Treated with Recombinant Poliovirus. N Engl J Med 2018; doi: 10.1056/NEJMoa1716435
Cancer prevention is the most significant reason for HPV vaccine acceptance
Parents rank cancer prevention as the most compelling reason for giving their children an HPV vaccine, a survey among 1,200 US parents of 11–17-year-olds revealed.1 The vaccine prevents most of HPV-induced cancer cases, yet less than half of US adolescents are up-to-date with the recommended vaccination schedule.
“Providers report giving a wide variety of reasons to vaccinate, but this study suggests what parents really want to hear about is cancer prevention. This was true even for parents who had relatively low confidence in adolescent vaccination,” lead author Melissa Gilkey of University of North Carolina said.
1. Gilkey MB, Zhou M, McRee AL, Kornides ML, Bridges JFP. Parents’ Views on the Best and Worst Reasons for Guideline-Consistent HPV Vaccination. Cancer Epidemiol Biomarkers Prev 2018; doi: 10.1158/1055–9965.EPI-17–1067
Pembrolizumab beneficial in lung, skin and prostate cancers
The PD-1 inhibitor pembrolizumab (Keytruda, Merck) extended survival of non-small cell lung cancer (NSCLC) patients in two clinical trials. In the first one, which enrolled > 1,200 subjects with advanced disease, the immunotherapeutic showed median survival of 16.7 months compared to 12.1 months in patients treated with chemotherapy. In the second trial, 560 patients with late-stage squamous NSCLC received pembrolizumab with chemotherapy or chemotherapy alone. The median survival was 15.9 and 11.3 months, respectively.
In the Phase 3 KEYNOTE-006 study, pembrolizumab showed durable efficacy in treatment of melanoma. 86% of experimental subjects were without tumor progression after a median of 20 months.
Finally, the checkpoint inhibitor showed some promise in men with untreatable advanced prostate cancer. Of 260 subjects in the trial, almost 40% were alive after one year and 5% reported tumor regression.
BCG vaccine can restore healthy blood sugar levels in type 1 diabetes
The BCG vaccine, routinely used for decades to immunize infants against tuberculosis, might be effective in treating type 1 diabetes, an autoimmune disease characterized by high sugar levels in the blood. In a Phase 1 study, 52 patients received two doses 4 weeks apart and saw their blood sugar restored to near-normal levels for eight years.1
The vaccine induces the formation of Tregs, which dampen autoimmune reactions, as well as a switch to aerobic glycolysis that leads to increased consumption of blood sugar. “BCG not only resets the immune response at the DNA level, but it also resets the metabolism for high sugar elimination,” senior author Denise Faustman of Massachusetts General Hospital told FierceBiotech.
1. Kühtreiber WM, Tran L, Kim T, Dybala M, Nguyen B, Plager S, Huang D, Janes S, Defusco A, Baum D, Zheng H, Faustman DL. Long-term reduction in hyperglycemia in advanced type 1 diabetes: the value of induced aerobic glycolysis with BCG vaccinations. NPJ Vaccines 2018; 3:23
A case of recurrent breast cancer completely eliminated by autologous T-cell transfer
A patient with metastatic breast cancer unresponsive to standard treatment had a complete remission after adoptive transfer of autologous tumor infiltrating lymphocytes (TILs).1 The response lasted for at least 22 months.
In the procedure tested in a Phase 2 clinical trial, researchers sequence complete DNA and RNA from the patient’s cancerous and healthy tissues, identify unique mutations, and expand in vitro autologous TILs specific to the neoepitopes. The cells are infused back to the patient along with the checkpoint inhibitor pembrolizumab to prevent immune evasion by the tumor.
1. Zacharakis N, Chinnasamy H, Black M, Xu H, Lu YC, Zheng Z, Pasetto A, Langhan M, Shelton T, Prickett T, Gartner J, Jia L, Trebska-McGowan K, Somerville RP, Robbins PF, Rosenberg SA, Goff SL, Feldman SA. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat Med 2018; 24(6):724–730
Ebola outbreak in Congo ‘largely contained’ after vaccination campaign
The most recent Ebola outbreak in the Democratic Republic of Congo has been ‘largely contained’ according to the World Health Organization. The outbreak has claimed 28 lives with 38 total confirmed cases.
Public health officials started a ring vaccination campaign one month earlier, in which the experimental Ebola vaccine rVSV-ZEBOV (Merck) was administered to people who interacted with an infected individual, and to their contacts. 3,200 people in the affected area have been vaccinated.
HPV-9 vaccine is reviewed for expansion of age indication
The 9-valent HPV vaccine Gardasil 9 (Merck) has been placed under priority review by the US Food and Drug Administration (FDA) for expansion of its use to include an older population. The vaccine is approved for people aged 9–26 years, and the FDA is considering approval for adults 27–45 years of age.
Recent data have shown that women in the latter age cohort are vulnerable to HPV infection by one of the nine targeted strains. The vaccine provides a long-term protection against most cases of infection that lead to HPV-associated cancers.
Ocrelizumab treatment leads to lower vaccine immunogenicity
The multiple sclerosis immunotherapeutic ocrelizumab (Ocrevus, Roche) decreased humoral responses to multiple vaccines.1 100 patients were randomized into ocrelizumab-treated and control groups and received a tetanus toxoid vaccine, keyhole limpet hemocyanin used as carrier in cancer vaccines, and the 23-valent pneumococcal polysaccharide vaccine. A subset of participants further received a seasonal influenza vaccine. Antibody titers to all antigens were decreased in the experimental group.
Ocrelizumab is a monoclonal antibody targeting the CD20 receptor on B lymphocytes to reduce demyelinating attacks in multiple sclerosis.
“While antibody responses were reduced in the ocrelizumab treated patients, they still responded to a certain level. This is valuable information in terms of seasonal vaccines such as the flu – it appears safe for patients taking ocrelizumab to get vaccinated and vaccination is likely to provide them with at least some protection from such infections,” senior author Amit Bar-Or of University of Pennsylvania said.
1. Stokmaier D, Winthrop K, Chognot C, Evershed J, Manfrini M, McNamara J, Bar-Or A. Effect of Ocrelizumab on Vaccine Responses in Patients With Multiple Sclerosis. Neurology 2018; 90
Experimental HIV vaccine is immunogenic for at least 6 months
Immune responses were maintained for 6 months after vaccination with the HIV vaccine Pennvax-GP (Inovio). The placebo-controlled Phase 1 trial enrolled almost 100 subjects, most of whom received the vaccine with the immune activator IL-12.
Pennvax-GP is a DNA vaccine encoding the env, gag and pol antigens of HIV-1. Earlier results from the same study reported > 90% immunogenicity with respect to CD4+, CD8+ and antibody responses.
Listeria-based immunotherapy is tested in solid cancers
Safety, immunogenicity and optimal dose of the neoadjuvant vaccine ADXS-NEO (Advaxis & Amgen) are being studied in a Phase 1 trial involving 50 subjects with solid tumors. ADXS-NEO is prepared by identifying cancer neoantigens via sequencing the patient’s healthy and tumor tissues, and cloning them into the attenuated Listeria monocytogenes. The bacterial vector has been shown to enhance immune responses against the antigen.
The indications tested include metastatic NSCLC, metastatic microsatellite stable colon cancer, and metastatic squamous head and neck cancer. ADXS-NEO induced T-cell responses in preclinical trials.
Cell-based influenza vaccines are similarly effective to traditional vaccines in the elderly
Seasonal influenza vaccines produced in cell culture provide ~ 25% protection in people aged ≥ 65 years, according to an FDA report. That is a rate of efficacy comparable to the one seen for traditional egg-based vaccines, which has been attributed to accumulating mutations in the influenza genomes during the manufacturing process in chicken eggs.
The study investigated hospitalizations due to influenza in > 13 million US Medicare beneficiaries. The cases were not necessarily confirmed in the laboratory, which might have led to underestimating of the vaccine’s effectiveness.