Early successes of two skin cancer immunotherapies
Two very-small-scale immunotherapy studies revealed potential new ways to treat melanoma. In the first one, a subject with multiple metastases was treated with adoptive transfer of peripheral blood-derived cytotoxic T cells stimulated with IL-21 in combination with the anti-CTLA-4 MAb ipilimumab. The patient experienced a complete remission and remained disease-free five years later.1
The second study administered a dendritic-cell (DC) vaccine to two melanoma patients whose tumor had spread to the liver. The vaccine was prepared from autologous DCs loaded with antigens from irradiated melanoma cells. One of the subjects had no disease progression for >4 years and was alive >8 years after treatment. The other went into complete remission and was alive >12 years later.2
Melanoma is the deadliest type of skin cancer when it metastasizes into other organs, with poor prognosis and limited treatment options.
| 1. | Chapuis AG, Lee SM, Thompson JA, Roberts IM, Margolin KA, Bhatia S, Sloan HL, Lai I, Wagener F, Shibuya K, Cao J, Wolchok JD, Greenberg PD, Yee C. Combined IL-21-primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient. J Exp Med 2016; doi: 10.1084/jem.20152021 | ||||
| 2. | Dillman RO. Long-Term Progression-Free and Overall Survival in Two Melanoma Patients Treated with Patient-Specific Therapeutic Vaccine Eltrapuldencel-T After Resection of a Solitary Liver Metastasis. Cancer Biother Radiopharm 2016; 31(3):71-4 | ||||
Influenza vaccination was found beneficial for pregnant women and patients with heart failure
Seasonal influenza vaccination during pregnancy reduced the risk of acute respiratory infections (ARI) in the mothers by >60%. The retrospective study, published in Vaccine,1 examined almost 35,000 Australian women, and found 10 and 36 ARI-related emergency department visits per 10,000 women in vaccinated and unvaccinated groups, respectively.
This work adds to previous observations that maternal influenza immunization is also beneficial for the newborn infants. Despite this, the authors found that <9% of the women received influenza vaccine during pregnancy.
In another study, influenza vaccination was associated with 30% lower risk of hospitalization for cardiovascular diseases. The effect was strongest for patients under the age of 66. This investigation involved data on almost 5 million UK residents between 1990 and 2013.
| 1. | Regan AK, Klerk N, Moore HC, Omer SB, Shellam G, Effler PV. Effectiveness of seasonal trivalent influenza vaccination against hospital-attended acute respiratory infections in pregnant women: A retrospective cohort study. Vaccine 2016; doi: 10.1016/j.vaccine.2016.05.032 | ||||
Dendritic cell vaccine combined with a tetanus toxoid boost improved prospects of glioblastoma patients
A small Phase 2 study revealed promise of a cytomegalovirus (CMV)-targeting DC vaccine in combination with tetanus toxoid immune boost, chemotherapy and radiation therapy in 11 patients with glioblastoma. Four of the subjects were progression-free at the time of analysis five years after treatment.
“Interestingly, patients receiving the tetanus before the CMV vaccine seemed to have much longer survival,” lead author Kristen Batich of Duke University told the media. “This may be related to the ability of tetanus to improve the migration of the CMV dendritic cell vaccine to local lymph nodes.”
Glioblastomas are susceptible to CMV infection, and >90% of cases express CMV antigens. The standard-of-care in glioblastoma patients is surgery followed by radiation and chemotherapy. Glioblastoma is one of the most aggressive and lethal cancers.
Improving recommendation can increase HPV vaccination rates
Researchers at Cincinnati Children's Hospital in Ohio saw an increase in HPV vaccine completion rates following interventions to improve provider's recommendations. After they performed a self-audit to determine the main barriers to vaccine completion and implemented a better recommendation system, they observed that the weekly rates of HPV vaccination on a scheduled visit increased from 80% to 92%, and the number of adolescents who returned only because of the next dose doubled.
“The significant finding from our project is that by solely improving vaccine recommendation in quality and frequency, we drastically improved our overall rates, and now over 60% of our 1000 teenagers have completed their HPV series, compared to 39% of females and 21% of males nationally,” lead author Landon Krantz said.
“This supports recent studies demonstrating that a lack of strong provider recommendation is a prominent barrier to vaccination. Therefore, just by giving a more effective and more timely vaccine recommendation, we significantly increased our population's HPV vaccination rates in only 10 months.”
Immunotherapy might overcome chemotherapy resistance of ovarian cancer
The widespread resistance to cisplatin chemotherapy in ovarian-cancer patients can be reversed by boosting the immune system, according to a study published in Cell.1 By linking cell types found in the tumor microenvironment to patient outcomes, the researchers found that fibroblasts are responsible for chemotherapy resistance by preventing platinum from accumulating in the tumor. This effect was overcome by IFN-γ-induced T cells in a mouse model.
Thus, combining T-cell-stimulating immunotherapy with standard-of-care chemotherapy might lead to better outcomes. “Then we could potentially go back to the same chemotherapy drug that we thought the patient was resistant to. Only now we have reversed that and it's effective again,” co-senior author Rebecca Liu said in a press release.
| 1. | Wang W, Kryczek I, Dostál L, Lin H, Tan L, Zhao L, Lu F, Wei S, Maj T, Peng D, He G, Vatan L, Szeliga W, Kuick R, Kotarski J, Tarkowski R, Dou Y, Rattan R, Munkarah A, Liu JR, Zou W. Effector T Cells Abrogate Stroma-Mediated Chemoresistance in Ovarian Cancer. Cell 2016; 165(5):1092-105 | ||||
RSV vaccine candidate promising in early trial
The RSV vaccine candidate MVA-BN RSV (Bavarian Nordic) was well tolerated and immunogenic in a Phase 1 trial. The pentavalent vaccine is designed to protect against both RSV subtypes. 63 healthy adults were divided into 3 groups: 50–65 years of age receiving high dose of the vaccine, and 18–50 years receiving high or low dose. All groups showed antibody production and mounted T-cell response.
There is no vaccine against RSV, which is one of the most common cause of lower respiratory tract infections among infants and older adults.
Atezolizumab approved in the U.S. for treatment of bladder cancer
The U.S. Food and Drug Administration has approved the anti-PD-L1 MAb atezolizumab (Tecentriq, Roche) in advanced urothelial carcinoma. The decision was based on a clinical study showing tumor shrinkage in 15% and complete remission in 5% of patients who received atezolizumab.
Atezolizumab is the fourth checkpoint inhibitor approved in the U.S. These MAbs block the PD-1 or the CTLA-4 pathways, both of which are exploited by tumors to inhibit the patient's immune response against them.
Malaria vaccine candidate offered protection in early trial
55% of healthy volunteers with no prior malaria infection were protected from the disease one year after administration of an investigational vaccine PfSPZ. The Phase 1 study enrolled 101 subjects aged 18–45 and tested the vaccine, which consists of live attenuated Plasmodium falciparum sporozoites, in 59 of them, either intravenously or intramuscularly.
“Administering the PfSPZ vaccine intravenously confers long-term, sterile protection in a small number of participants, which has not been achieved with other current vaccine approaches,” Robert Seder of the National Institute of Allergy and Infectious Diseases (NIAID) said in a statement.
A proof-of-principle study shows cancer immunotherapy using heterologous T cells
Cancer neoantigens can be recognized by healthy donors' T cells, whose receptors can subsequently help fight a tumor in patients. According to a study published in Science,1 heterologous T cells were able to recognize patient-derived melanoma neoantigens, and the receptors thus generated could be used to engineer patients' own immune cells to attack the tumor. This strategy can be used in cases, in which the autologous tumor-infiltrating lymphocytes isolated from the patient fail to recognize the cancer neoantigens.
“Our study shows that the principle of outsourcing cancer immunity to a donor is sound,” co-senior author Johanna Olweus University of Oslo said in a press release. “However, more work needs to be done before patients can benefit from this discovery. Thus, we need to find ways to enhance the throughput. We are currently exploring high-throughput methods to identify the neo-antigens that the T cells can “see' on the cancer and isolate the responding cells.”
| 1. | Strønen E, Toebes M, Kelderman S, van Buuren MM, Yang W, van Rooij N, Donia M, Böschen ML, Lund-Johansen F, Olweus J, Schumacher TN. Targeting of cancer neoantigens with donor-derived T cell receptor repertoires. Science 2016; doi: 10.1126/science.aaf2288 | ||||
Dramatic decrease in rotavirus-related hospitalizations after the launch of universal vaccination
>70% drop in hospitalizations due to rotavirus (RV) infection followed the introduction of a universal vaccination program in Ontario, Canada. The study1 analyzed >860,000 hospital records related to RV infections and acute gastroenteritis both before and after the start of the program in 2011. Both child and adult emergency department visits decreased considerably, suggesting herd immunity protected unvaccinated individuals, too.
“We expected to see a drop for babies and toddlers who were vaccinated under this program,” lead author Sarah Wilson of University of Toronto said in a statement. “What's particularly interesting is we saw the drop even in older kids who were too old to receive the publicly funded rotavirus vaccine, which means that protecting babies against illness also benefited older children.”
Acute gastroenteritis caused by RV leads to vomiting, diarrhea, fever, abdominal pain, and sometimes severe dehydration. 7% of infected Canadian children require hospitalization. Moreover, the virus is highly contagious and spreads easily in the family.
| 1. | Wilson SE, Rosella LC, Wang J, Le Saux N, Crowcroft NS, Harris T, Bolotin S, Deeks SL. Population-Level Impact of Ontario's Infant Rotavirus Immunization Program: Evidence of Direct and Indirect Effects. PLOS One 2016; doi: 10.1371/journal.pone.0154340 | ||||
Prostate cancer vaccine enters a Phase 2 trial
A therapeutic prostate cancer vaccine ProscaVax (OncBioMune) will enroll patients with previously untreated prostate cancer in a Phase 2 clinical trial. A previous Phase 1 study in 8 subjects with recurrent or hormone-refractory cancer demonstrated increased immune responses and reduction in disease progression. The vaccine contains prostate-specific antigen whole protein plus interleukin-2 and granulocyte macrophage–colony stimulating factor as adjuvants.
Developments toward Zika vaccine
Two Zika vaccine candidates might enter clinical trials this year. Inovio's candidate elicited robust antibody and T-cell responses in nonhuman primates. It is an intramuscularly administered synthetic DNA vaccine encoding multiple Zika antigens.
The second candidate from Pharos Biologicals is based on the lysosome-associated membrane protein DNA vaccine technology, in which the antigen is fused with a natural lysosomal glycoprotein to facilitate antigen presentation.
Zika infection in pregnancy has been linked with microcephaly in newborns. The epidemic, which has affected mainly Latin American and Asian countries, is thought to put half a billion people at risk.