Cancer immunotherapy outcome might be affected by gender and cholesterol levels
Survival benefit from checkpoint immunotherapy in men is twice as high as that in women, according to a meta-analysis of 20 randomized trials involving a total of > 11,000 patients with advanced cancers.1 The difference might be accounted for by stronger average immune responses mounted by women as well as interactions between genes, hormones, environment and microbiome composition. The authors also note underrepresentation of women in clinical trials, which might lead to false conclusions about efficacy and safety, thus resulting in poorer health care.
In another study, lowering cholesterol improved the anti-tumor effect of adoptive T-cell transfer therapy in a preclinical model.2 The treatment increased IL-9 secretion, which had been shown to potentiate the immunotherapeutic effect of T cells. “Our studies suggest a relatively simple, cost effective way to enhance T-cell transfer therapy,” senior author Qing Yi of Cleveland Clinic said.
- Conforti F, Pala L, Bagnardi V, De Pas T, Martinetti M, Viale G, Gelber RD, Goldhirsch A. Cancer immunotherapy efficacy and patients' sex: a systematic review and meta-analysis. Lancet Oncol 2018; doi: 10.1016/S1470-2045(18)30261-4
- Ma X, Bi E, Huang C, Lu Y, Xue G, Guo X, Wang A, Yang M, Qian J, Dong C, Yi Q. Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity. J Exp Med 2018; doi: 10.1084/jem.20171576
No link found between the 4-valent HPV vaccine and autoimmune disease
Girls vaccinated with the 4-valent HPV vaccine (Gardasil, Merck) are no more likely to develop an autoimmune disease than the general population, according to a study that reviewed data on 290,000 girls aged 12–17 between 2007–13.1 Among the 180,000 girls who received at least one dose, 680 were diagnosed with an autoimmune disease one week to two months later, which is consistent with the rate of diagnosis in this age group.
“These findings add to the body of evidence on the safety of the HPV4 vaccine and should reassure parents and health care providers,” senior author Linda Lévesque said.
- Liu EY, Smith LM, Ellis AK, Whitaker H, Law B, Kwong JC, Farrington P, Lévesque LE. Quadrivalent human papillomavirus vaccination in girls and the risk of autoimmune disorders: the Ontario Grade 8 HPV Vaccine Cohort Study. CMAJ 2018; 190(21):E648–E655
DC vaccine improves survival in glioblastoma patients
An autologous dendritic cell (DC) vaccine DCVax-L (Northwest Bio) increased survival in adults with newly diagnosed glioblastoma.1 The 331 patients in the Phase 3, who were treated with the standard-of-care surgery, chemo – and radiotherapy plus DCVax-L or placebo, showed a combined median survival of 23 months compared to 15–17 months typically following standard-of-care treatment of glioblastoma. The rate of adverse events was small and comparable to that of standard therapy. DCVax-L consists of a patient's own DCs pulsed with the tumor lysate.
- Liau LM, Ashkan K, Tran DD, Campian JL, Trusheim JE, Cobbs CS, Heth JA, Salacz M, Taylor S, D'Andre SD, Iwamoto FM, Dropcho EJ, Moshel YA, Walter KA, Pillainayagam CP, Aiken R, Chaudhary R, Goldlust SA, Bota DA, Duic P, Grewal J, Elinzano H, Toms SA, Lillehei KO, Mikkelsen T, Walpert T, Abram SR, Brenner AJ, Brem S, Ewend MG, Khagi S, Portnow J, Kim LJ, Loudon WG, Thompson RC, Avigan DE, Fink KL, Geoffroy FJ, Lindhorst S, Lutzky J, Sloan AE, Schackert G, Krex D, Meisel HJ, Wu J, Davis RP, Duma C, Etame AB, Mathieu D, Kesari S, Piccioni D, Westphal M, Baskin DS, New PZ, Lacroix M, May SA, Pluard TJ, Tse V, Green RM, Villano JL, Pearlman M, Petrecca K, Schulder M, Taylor LP, Maida AE, Prins RM, Cloughesy TF, Mulholland P, Bosch ML. First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J Transl Med 2018; 16(1):142
Doctors’ persistence might increase vaccine uptake
Repeated recommendations to vaccinate their children can change the mind of a hesitant parent, a study suggests.1 The team recorded 43 doctor visits by parents of adolescents eligible for HPV vaccination. Of the 37 instances in which parents expressed concern and hesitancy, 18 were followed by doctor's persistence in recommending the vaccine. In this case, 94% of adolescents ended up being vaccinated, compared to 0% and 15% when the doctor's response was acquiescence or the mix of the two, respectively.
The HPV immunization rate is ∼ 60% in the US despite the recommendation to vaccinate all children aged 11–12 years. According to the authors, doctors’ lack of persistence is a missed opportunity to boost acceptance.
- Shay LA, Baldwin AS, Betts AC, Marks EG, Higashi RT, Street RL Jr, Persaud D, Tiro JA. Parent-Provider Communication of HPV Vaccine Hesitancy. Pediatrics 2018; 141(6)
Subcutaneous immunotherapy against house-dust mite allergy passes early trial
The tyrosine-adsorbed house-dust mite vaccine (Allergy Therapeutics) ameliorated symptoms in a Phase 1 trial involving 140 patients in Spain. The immunotherapeutic, which is administered with a monophosphoryl lipid A adjuvant derived from Salmonella lipopolysaccharides, demonstrated a 43% decrease in combined symptom medication score after one year compared to baseline. Additionally, 17% of asthmatic patients reported persistent asthma compared to 51% at baseline.
CMV vaccine candidate showed promising data in a Phase 1 trial
The cytomegalovirus (CMV) vaccine VBI-1501 (VBI Vaccines) elicited neutralizing antibodies against fibroblast infection in 100% of people who received the highest dose in a dose-escalation, three-dose, placebo-controlled Phase 1 study. 30% of subjects developed antibodies that neutralize epithelial cell infection, which is more difficult to protect against. All doses were well tolerated.
VBI-1501 is an enveloped virus-like particle (VLP) presenting modified glycoprotein B from CMV. While most infected people show no symptoms, CMV can be dangerous when transmitted vertically during pregnancy or horizontally from transplanted organ to its new immunosuppressed host. ∼ 5,000 US infants have birth defects due to CMV infection annually. The goal of the clinical program is to administer VBI-1501 to pregnant women or women of childbearing age.
Investigational Ebola vaccine is used to fight an outbreak in Congo
The Ebola vaccine rVSV-ZEBOV (Merck) has been approved by the Health officials in Congo for use in emergency settings. The recent outbreak in the northeast of the country has killed four people and is suspected to have infected > 50 others.
rVSV-ZEBOV has not been formally approved, but it elicited a high rate of protection in clinical trials. In the so-called ring vaccination approach, it will be administered to people who interacted with an infected individual, and to their contacts.
Chikungunya vaccine fast-tracked by FDA
The US Food and Drug Administration (FDA) has granted its fast-track designation to a chikungunya vaccine candidate (PaxVax), based on promising Phase 2a clinical data obtained at the National Institutes of Health. A Phase 2b trial is underway, enrolling 400 participants to determine optimal dose.
The vaccine is a VLP, which mimics the natural form of the virus without its genetic content. The mosquito-borne chikungunya virus is a serious public health concern in the tropics. No vaccine is available for preventing the infection.
Gardasil 9 received a conditional approval in China
Chinese officials have approved the 9-valent HPV vaccine Gardasil 9 (Merck), provided that additional studies and postmarketing surveillance will be carried out. Large-scale international trials have shown that Gardasil 9 prevents > 90% of cervical, vulvar and vaginal cancer cases.
The vaccine was approved in US and Europe in 2014 and 2015, respectively. High demand led to a recent shortage in several countries.
New RSV vaccine enters clinical testing
A placebo-controlled Phase 1/2 trial will investigate safety and immunogenicity of a respiratory syncytial virus (RSV) vaccine candidate (Pfizer) in ∼ 1,200 adult participants. The subjects will be divided into two age cohorts (18–49 and 50–85 years) and receive one of six formulations with or without concomitant inactivated influenza vaccine. The RSV vaccine is designed to protect infants via maternal immunization or to directly protect elderly subjects from infection.
RSV infection is a global health priority affecting mostly young children and older adults. Of the > 30 million annual cases in children under 5 years of age, 120,000 die. There is no licensed RSV vaccine.