Personalized vaccine might improve checkpoint blockade immunotherapy
Immunization with the neoantigen vaccine NEO-PV-01 (Neon Therapeutics) extended survival in patients with skin, bladder and lung cancer being treated with the PD-1 inhibitor nivolumab (Opdivo, BMS). The Phase 1b NT-001 study enrolled 82 subjects with advanced disease at various stages of conventional treatment and reported median progression-free survival of 5.6 months after one year for bladder cancer and non-small cell lung cancer (NSCLC), compared with ~3 months seen in historical control data for nivolumab treatment alone. Median progression-free survival has not been reached in melanoma patients.
In the NEO-PV-01 program, patients’ tumors are sequenced, and upon identification of candidate neoantigens, a vaccine is formulated as synthetic peptides.
Single dose of HPV vaccine is sufficient in preventing precancerous cervical lesions
One dose of the 4-valent HPV vaccine showed comparable effectiveness in preventing cervical intraepithelial neoplasia or cancer as full three-dose regimen in a retrospective study of 250,000 Australian women between 2007 and 2014.Citation1 The risk of a positive Pap smear test was decreased by 35%, 39% and 41% following one-, two- and three-dose vaccination, respectively, compared to unvaccinated subjects.
Although coming from a high-coverage country, the results are significant particularly for the developing world, where there is high burden of cervical cancer and often limited access to vaccines. The finding might also facilitate reaching the World Health Organization (WHO)’s goal of global elimination of cervical cancer announced in 2018.
CAR-T cell therapy can be used to fight solid tumors
60% of mice saw their solid tumors cleared after chimeric-antigen receptor (CAR)-T cell therapy combined with a lymph node-directed vaccine.Citation2 In CAR-T therapy, which has so far been successful only in blood cancers, the patient’s own T cells are engineered to target a tumor-specific neoantigen. The vaccine in turn consists of the neoantigen linked to a lipid, which binds to albumin and is thereby transported to lymph nodes. The vaccine potently induced CAR-T cell expansion leading to 65% of the animals’ total T cell population consisting of the CAR-T cells. The procedure successfully treated glioblastoma, melanoma and breast cancer, and also cleared tumor cells re-injected into these mice, even those that did not express the neoantigen.
A similar CAR-T technology (NeoTCR-P1, Pact Pharma), based on tumor sequencing, harvesting neoantigen-specific T cells from patients’ blood and engineering synthetic receptors, has started a Phase 1 trial with melanoma patients.
France and Italy saw increased vaccine uptake after making several vaccines mandatory
Meningococcal C vaccine coverage among French infants increased from 39% to 76% in the first five months of 2018 compared to the same period one year earlier.Citation3 This uptick, which translated into a decrease of annual meningitis C cases from 17 in the period 2012–6 to 4 in 2018, follows a change in vaccination laws, which extended the list of mandatory vaccines by eight, including hepatitis B and pneumococcal vaccines.
Italy made six more pediatric vaccines mandatory after a large outbreak of measles in 2017 and reported that 94% of children <30 months had received the measles vaccine by mid-2018, compared to 87% of two-year-olds in 2016.Citation4 Both countries also registered increased uptake of voluntary vaccines, likely due to information campaigns.
Targeting tumor-associated macrophages might sensitize pancreatic cancer to immunotherapy
Stimulating surface integrins (CD11b) reprogrammed tumor-associated macrophages to reduce tumor growth and engage T-cell immunity in a mouse model of pancreatic cancer.Citation5 Moreover, treatment with the CD11b agonist ADH-503 led to tumor shrinkage and longer survival after anti-PD-1 immunotherapy, which has been so far unsuccessful in treating pancreatic cancer.
“Pancreatic cancer is a highly lethal disease and we are in desperate need of new therapeutic approaches. In animal studies, this small molecule [ADH-503] led to very marked improvements and was even curative in some cases. We are hopeful that this approach could help pancreatic cancer patients,” senior author David DeNardo of Washington University in St. Louis said.
HPV vaccination program in the UK is expanded to both sexes
All boys aged 11–13 in the UK will be offered HPV vaccine for free, 11 years after the program started for girls. Officials expect this will prevent almost 30,000 of penile, anal and head-and-neck cancer cases in the next 40 years.
While women up to 25 years of age are eligible for a catch-up dose, older boys are not included in the program, except for gay men who can get vaccinated up to the age of 45.
Long-term clinical benefits of nivolumab reported for three cancer types
Durable responses and relatively high long-term survival rates were observed in a study that followed 270 adult cancer patients following nivolumab treatment.Citation6 The five-year survival rates were 34%, 28% and 16% for subjects with advanced melanoma, renal cell carcinoma and NSCLC, respectively, compared to 5% for melanoma and 6% for NSCLC following conventional therapies.
“While all patients had been treated previously, the number of prior treatments did not make a statistical difference in terms of five-year survival in this study,” lead author Suzanne Topalian of Johns Hopkins University said. However, survival was significantly longer in patients who experienced adverse events in response to nivolumab.
Marburg virus vaccine candidate provided 100% protection in a preclinical trial
All guinea pigs vaccinated with the Marburg virus vaccine GEO-EM05 (GeoVax) survived a lethal-dose challenge at least 21 days with no weight loss or health issues. In contrast, all animals in a placebo group had to be euthanized due to terminal-stage illness within 8 days post-challenge.
GEO-EM05 consists of Marburg virus antigens carried by the Modified Vaccinia Ankara virus-like particles, which are non-infectious but trigger robust and durable immune responses. There are no vaccines for Marburg virus or treatment for the Marburg hemorrhagic fever.
Ebola outbreak in the Democratic Republic of the Congo was declared ‘international emergency’
The second largest Ebola outbreak in history, which has ravaged the Democratic Republic of the Congo since August 2018 killing at least 1,700 people, has been declared as international emergency by WHO. Health-care workers have administered 170,000 doses of the vaccine rVSV-ZEBOV-GP (Merck), but they face public distrust and even violence, reporting 200 attacks in 2019 alone.
The vaccine, although unlicensed, is >97% effective according to preliminary data. However, anticipated shortage has led to international calls for the introduction of the second vaccine, Ad26.ZEBOV/MVA-BN (J&J), which has been rejected by the country’s Health Minister Oly Ilunga Kalenga due to unproven effectiveness. Nonetheless, Kalenga has resigned under pressure, and the manufacturer announced that 1.5 million doses are ready for deployment.
Engineered bacteria deliver immunotherapeutics into tumors
Complete lymphoma regression in a mouse model was reported after local delivery and proliferation of non-pathogenic Escherichia coli releasing an anti-CD47 nanobody.Citation7 CD47 is overexpressed in many solid tumors, leading to inhibition of macrophages and DCs. The nanobody combines with inflammation caused by the bacteria to induce an anti-tumor immune response without the toxicity seen in systemic administration of CD47 antagonists.
“Treatment with engineered bacteria led to priming of tumor-specific T cells in the tumor that then migrated systemically to also treat distant tumors. Without both live bugs lysing in the tumor and the CD47 nanobody payload, we were not able to observe the therapeutic or abscopal effects,” senior author Nicholas Arpaia of Columbia University said.
Mosaic HIV vaccine enters Phase 3 clinical testing
A broad-range HIV vaccine is tested in the Americas and Europe. The placebo-controlled study, which enrolls 3,800 transgender and gay men who are at high risk of contracting the infection, will test four doses in the course of one year.
The adenovirus-vectored ‘mosaic’ vaccine, which carries three gene composites generated from multiple HIV strains from around the world, induced immune responses lasting at least two years in previous trials. >100 HIV vaccines have been tested so far, and only one has had any protective effect, which lasted for a very short period of time.
References
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- Ma L, Dichwalkar T, Chang JYH, Cossette B, Garafola D, Zhang AQ, Fichter M, Wang C, Liang S, Silva M, et al. Enhanced CAR–T cell activity against solid tumors by vaccine boosting through the chimeric receptor. Science. 2019;365(6449):162–68. doi:10.1126/science.aav8692.
- Lévy-Bruhl D, Fonteneau L, Vaux S, Barret AS, Antona D, Bonmarin I, Che D, Quelet S, Coignard B. Assessment of the impact of the extension of vaccination mandates on vaccine coverage after 1 year, France, 2019. Euro Surveill. 2019. doi:10.2807/1560-7917.ES.2019.24.26.1900301.
- D’Ancona F, D’Amario C, Maraglino F, Rezza G, Iannazzo S. The law on compulsory vaccination in Italy: an update 2 years after the introduction. Euro Surveill. 2019. doi:10.2807/1560-7917.ES.2019.24.26.1900371.
- Panni RZ, Herndon JM, Zuo C, Hegde S, Hogg GD, Knolhoff BL, Breden MA, Li X, Krisnawan VE, Khan SQ, et al. Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies. Sci Transl Med. 2019. doi:10.1126/scitranslmed.aau9240.
- Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Sosman JA, Atkins MB, Leming PD, et al. Correlates among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer treated with nivolumab. JAMA Oncol. 2019. doi:10.1001/jamaoncol.2019.2187.
- Chowdhury S, Castro S, Coker C, Hinchliffe TE, Arpaia N, Danino T. Programmable bacteria induce durable tumor regression and systemic antitumor immunity. Nat Med. 2019;25(7):1057–63. doi:10.1038/s41591-019-0498-z.