Clinical trials for SARS-CoV-2 vaccines have commenced
Around 50 vaccines against COVID-19 are in early development, according to Fierce Pharma. The most advanced candidate, mRNA-1273 (Moderna), entered Phase 1 clinical testing only two months after the publication of the SARS-CoV-2 genomic sequence. The U.S. National Institutes of Allergy and Infectious Diseases trial is enrolling 45 healthy adults aged 18–55 years and evaluating safety and immunogenicity of different doses administered in two injections four weeks apart.
Another vaccine entering clinical trials is a SARS-CoV-2 spike protein-targeting, chimpanzee adenovirus-vectored ChAdOx1. The safety and immunogenicity study is being carried out at the University of Oxford.
Two additional mRNA vaccine platforms will be employed against the novel coronavirus. BNT162 (BioNTech & Pfizer), which grew out of a vaccine candidate for the prevention of influenza, is scheduled to enter clinical trials in 2Q20. A collaboration between Sanofi and Translate Bio will test multiple constructs in their mRNA platform.
J&J in collaboration with the U.S. Department of Health and Human Services is testing an adenovirus Ad26-vectored DNA vaccine in non-human primates. The technology has been tested in ~50,000 people in the development of vaccines for Ebola, HIV, RSV and Zika viruses.
Finally, a DNA vaccine INO-4800 (Inovio) is scheduled to start a Phase 1 trial in 2Q20. The candidate is related to a vaccine for MERS-CoV, which however has not gone through full clinical development.
The COVID-19 pandemic, which has spread to all corners of the world, has required drastic public-health measures affecting daily lives of billions of people as well as the global economy.
Prevnar-20 succeeds in a late-stage trial
The 20-valent pneumococcal conjugate vaccine Prevnar-20 (Pfizer) completed clinical trials and is ready for regulatory application. In a randomized, double-blind Phase 3 study conducted in almost 4,000 adults 18 years and older, Prevnar-20 elicited non-inferior immune responses against 13 pneumococcal strains targeted by its 13-valent predecessor Prevnar-13 in a direct comparison, and against 6 of the 7 remaining strains compared to 23-valent polysaccharide vaccine Pneumovax 23 (Merck). Safety objectives were also met.
In the Prevnar vaccines, capsule saccharides from Streptococcus pneumoniae are individually conjugated to inactivated diphtheria toxin. The bacterium causes invasive pneumococcal disease and meningitis, especially in children and older adults.
Immunotherapy combination holds promise for advanced prostate cancer patients
The cancer vaccine VTP-800 (Vaccitech) combined with the PD-1 inhibitor pembrolizumab (Merck) induced a ≥ 50% reduction in the tumor biomarker prostate-specific antigen (PSA) in five of 23 patients with metastatic castration-resistant prostate cancer. One subject had no detectable PSA after 24 weeks.
VTP-800 consists of the oncofetal antigen 5T4 encoded by chimpanzee adenovirus as a prime and Modified Vaccinia Ankara as a booster four weeks later. The Phase 2a ADVANCE study also administered pembrolizumab in three doses.
Recombinant influenza vaccine passes phase 3 trial
The nanoparticle influenza vaccine NanoFlu (Novavax) induced non-inferior antibody responses compared to Fluzone Quadrivalent (Sanofi) in a Phase 3 trial that enrolled >2,500 older U.S. adults and assessed immunogenicity four weeks post-vaccination. The vaccine was well tolerated.
NanoFlu consists of the viral hemagglutinin protein produced in a baculoviral expression system. It is administered with the Matrix-M adjuvant. Both NanoFlu and Fluzone used in the study targeted influenza strains recommended for the 2019–20 season in the Northern Hemisphere.
CAR-T therapy eradicates solid tumors in a preclinical study
Recombinant chimeric antigen receptor T cell (CAR-T) technology targeting glypican-1, which is overexpressed in several solid cancers, eradicated tumors in four out of five mice with colon adenocarcinoma for at least 100 days.Citation1 Furthermore, the combination with a PD-1 inhibitor potentiated the anti-tumor response by the CAR-T cells.
While most CAR-T studies use xenogeneic mouse models, in which human tumor is grafted onto the animal, researchers developed a syngeneic model in the present study, which allowed them to determine that the treatment was safe.
“By establishing a new type of model, we were able to test both the effectiveness, safety and anti-tumor mechanisms of CAR-T cells, showing the importance of choosing the most appropriate models for evaluating these novel types of cancer treatment,” senior author Yutaka Kawakami of Keio University said.
Reference
- Kato D, Yaguchi T, Iwata T, Katoh Y, Morii K, Tsubota K, Takise Y, Tamiya M, Kamada H, Akiba H, et al. GPC1 specific CAR-T cells eradicate established solid tumor without adverse effects and synergize with anti-PD-1 Ab. Elife. 2020. doi:10.7554/eLife.49392.