New developments in checkpoint-inhibition MAb immunotherapy
Three new approvals broaden the indications for immunotherapeutic MAbs targeting the PD-1 checkpoint pathway. Atezolizumab (Tecentriq, Roche) was approved in the EU for locally advanced or metastatic non-small cell lung cancer (NSCLC) and urothelial carcinoma, and avelumab (Bavencio, Merck & Pfizer) will become the first immunotherapy to treat metastatic Merkel cell carcinoma. Pembrolizumab (Keytruda, Merck) was approved by US Food and Drug Administration (FDA) for gastric or gastroesophageal junction cancer.
Pembrolizumab, which thus becomes the first gastric cancer immunotherapy with US license, was also found safe and ∼60% effective in combination with the oncolytic virotherapy talimogene laherparepvec (T-vec) in treating metastatic melanoma.Citation1 Clinical data from the Phase 1b trial with 21 patients suggested that the combination might be more effective than either drug as a monotherapy.
Finally, an anti-PD-1 MAb combined with TLR7 and TLR9 agonists as adjuvants elicited tumor-specific T-cell response and successfully eliminated both primary and metastatic tumors.in a mouse model of head-and-neck cancer.Citation2
- Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, Kirkwood JM, Gajewski TF, Chen L, Gorski KS, Anderson AA, Diede SJ, Lassman ME, Gansert J, Hodi FS, Long GV. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell. 2017;170(6):1109–1119.e10
- Sato-Kaneko F, Yao S, Ahmadi A, Zhang SS, Hosoya T, Kaneda MM, Varner JA, Pu M, Messer KS, Guiducci C, Coffman RL, Kitaura K, Matsutani T, Suzuki R, Carson DA, Hayashi T, Cohen EE. Combination immunotherapy with TLR agonists and checkpoint inhibitors suppresses head and neck cancer. JCI Insight. 2017;2(18)
Cell-based influenza vaccine superior in young children in a Phase 3 study
The only approved cell-based influenza vaccine, quadrivalent MF59-adjuvanted Flucelvax (Seqirus), showed 30 percentage points higher protection than a non-adjuvanted comparator quadrivalent vaccine in children aged ≤2 years, as measured by hemagglutination inhibition antibody titer. The Phase 3 trial, which spanned two seasons during 2013–5, enrolled >10,000 participants aged 6 months to 6 years. Flucelvax already offered better protection in all age groups after the first of two doses.
“Influenza and its complications pose a serious public health threat to young children, especially those under 2 years of age,” lead researcher Timo Vesikari of University of Tampere said. “Because standard influenza vaccines are less efficient in producing a robust immune response in young children, improved vaccines are urgently needed.”
Indian rotavirus vaccine successful in a large-scale trial
The rotavirus (RV) vaccine Rotasiil (Serum Institute of India) prevented 40% of severe RV diarrhea in a randomized, placebo-controlled Phase 3 trial with 7,500 Indian infants. The most severe RV cases were reduced by 55%.Citation1 Almost 4 million doses of Rotasiil have been ordered by the Indian government, which plans to launch a global immunization program. The pentavalent oral vaccine also awaits prequalification by the World Health Organization, which would enable global use.
- Kulkarni PS, Desai S, Tewari T, Kawade A, Goyal N, Garg BS, Kumar D, Kanungo S, Kamat V, Kang G, Bavdekar A, Babji S, Juvekar S, Manna B, Dutta S, Angurana R, Dewan D, Dharmadhikari A, Zade JK, Dhere RM, Fix A, Power M, Uprety V, Parulekar V, Cho I, Chandola TR, Kedia VK, Raut A, Flores J; SII BRV-PV author group. A randomized Phase III clinical trial to assess the efficacy of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants. Vaccine. 2017; doi: 10.1016/j.vaccine.2017.09.014
Novel chickenpox vaccine highly efficacious in a Phase 3 trial
A varicella zoster vaccine candidate (Sinovac) showed 87% efficacy in preventing chickenpox among 6,000 Chinese children aged 1–12 years, according to preliminary results of a randomized, placebo-controlled Phase 3 clinical trial, in which the experimental group received one dose of the vaccine prior to the 2016 chickenpox epidemic. In a parallel study, lot consistency was demonstrated on a group of 1,200 children aged 1–3 years.
RSV vaccine candidate elicits persistent immunogenicity
Persistent antibody response against several respiratory syncytial virus (RSV) epitopes was found six months after a Phase 2 trial with the MVA-BN RSV vaccine (Bavarian Nordic). The study enrolled >400 healthy adults 55 years of age or older to look at safety and immunogenicity of the vaccine, which is designed to protect against both A and B subtypes of RSV. The candidate will be tested in a human challenge study in 2018.
US experts recommend a new vaccine against shingles
The shingles vaccine Shingrix (GSK) is one step closer to clinical use based on an FDA expert panel having unanimously endorsed its approval. The indication, based on trial results showing long-lasting protection and higher rate of efficacy than the currently licensed vaccine, is for people aged ≥50 years.
Shingles, caused by the varicella zoster virus, affects mainly the elderly population. It is characterized by a painful skin rash with complications such as vision impairment and secondary infections.
Chikungunya vaccine candidate entered clinical trial
An mRNA vaccine against the Chikungunya virus, mRNA-1388 (Moderna), is being tested for safety and immunogenicity in a randomized, placebo-controlled, dose-ranging Phase 1 trial involving 60 healthy volunteers.
Mosquito-borne Chikungunya infection, which causes fever and joint pain or arthritis, is a concern mostly in tropical climates, but recently has spread to the US and Europe.
Microparticles could carry multiple doses in a single injection
A new 3D fabrication method successfully created a microparticle for sequential release of vaccines and other drugs.Citation1 The StampEd Assembly of polymer Layers (SEAL) technique creates particles with built-in pH sensors and microfluidic devices. The hope is that it will make possible combining different vaccines into a single dose administered at birth, which would be particularly beneficial for residents of developing countries with limited access to healthcare facilities.
“For the first time, we can create a library of tiny, encased vaccine particles, each programmed to release at a precise, predictable time, so that people could potentially receive a single injection that, in effect, would have multiple boosters already built into it. This could have a significant impact on patients everywhere, especially in the developing world where patient compliance is particularly poor,” senior author Robert Langer of MIT said.
- McHugh KJ, Nguyen TD, Linehan AR, Yang D, Behrens AM, Rose S, Tochka ZL, Tzeng SY, Norman JJ, Anselmo AC, Xu X, Tomasic S, Taylor MA, Lu J, Guarecuco R, Langer R, Jaklenec A. Fabrication of fillable microparticles and other complex 3D microstructures. Science. 2017;357(6356):1138-1142
Trivalent neutralizing antibodies might be effective against HIV
A trispecific broadly neutralizing antibody (bnAb) conferred complete protective immunity to a mixture of SHIV strains in non-human primates.1 The bnAb, which targets the CD4 binding site, the membrane-proximal external region and the V1V2 glycan site, outperformed monovalent bnAbs in a challenge experiment. Preparations for a Phase 1 clinical trial with HIV patients are underway.