Checkpoint inhibition immunotherapy proves efficient in rare type of skin cancer
70% of 60 patients with advanced desmoplastic melanoma responded to PD-1 pathway blockade. 19 subjects showed a complete response with no recurrence after five years.Citation1 Biomarker analysis revealed high PD-L1 expression in the desmoplastic melanoma tumors and high CD8+ density. Patients in this study received a variety of MAbs targeting PD-1 or PD-L1.
Desmoplastic melanoma is a rare type of cancer associated with dense fibrotic tissue, which makes it resistant to chemotherapy, radiation and surgery. It was thought to be resistant to immunotherapy as well due to the limited ability of immune cells to infiltrate the tumor environment.
- Eroglu Z, Zaretsky JM, Hu-Lieskovan S, Kim DW, Algazi A, Johnson DB, Liniker E, Ben Kong, Munhoz R, Rapisuwon S, Gherardini PF, Chmielowski B, Wang X, Shintaku IP, Wei C, Sosman JA, Joseph RW, Postow MA, Carlino MS, Hwu WJ, Scolyer RA, Messina J, Cochran AJ, Long GV, Ribas A. High response rate to PD-1 blockade in desmoplastic melanomas. Nature 2018; 18;553(7688):347–350.
Affordable rotavirus vaccine received WHO prequalification
The World Health Organization (WHO) has granted its prequalification to the rotavirus vaccine Rotavac (Bharat Biotech). International agencies will thus be able to use the vaccine in developing countries. Rotavac is cheaper than the other two vaccines in use, Rotarix (GSK) and RotaTeq (Merck), and the company said it could produce 200 million doses per year.
Rotavirus is the most common cause of severe diarrhea in children, particularly in the developing world. Around half a million children aged <5 years die every year.
The development of remote-controlled CAR-T cells
A novel ultrasound-based approach was reported that might allow for localized activation of chimeric antigen receptor T-cell (CAR-T) immunotherapy.Citation1 T-cells were engineered to express the Piezo1 mechano-sensor, which was designed to trigger a signaling cascade resulting in induction of the cancer-specific chimeric receptor. Researchers also coated the cells with microbubbles that vibrate upon exposure to ultrasound waves, which triggers the Piezo1 sensor.
This non-invasive approach could improve the precision of CAR-T treatment, in which targeting healthy issue is a common side effect.
- Pan Y, Yoon S, Sun J, Huang Z, Lee C, Allen M, Wu Y, Chang YJ, Sadelain M, Shung KK, Chien S, Wang Y. Mechanogenetics for the remote and noninvasive control of cancer immunotherapy. Proc Natl Acad Sci U S A 2018; 115(5):992–997.
New shingles vaccine recommended by a European committee
The European Medicines Agency's Committee for Medicinal Products for Human Use has recommended approval of the shingles vaccine Shingrix (GSK) for prevention of herpes zoster and post-herpetic neuralgia in adults ≥50 years. The vaccine was previously approved in Canada and US.
Shingrix, which is an adjuvanted formulation of recombinant varicella zoster virus glycoprotein E, showed a higher level of protection (≥90%) than the other licensed vaccine Zostavax (Merck) in clinical trials, especially in the older age groups, although the two vaccines have not been compared in the same trial.
Immune markers might predict success of checkpoint immunotherapy
Immune cell characterization by single-cell mass cytometry predicted response to PD-1 immunotherapy in melanoma patients. According to the study, the strongest predictor of progression-free and overall survival was the frequency of CD14+CD16−HLA-DRhi monocytes.Citation1 A large portion of cancer patients do not show durable responses to checkpoint blockade, yet have to withstand serious adverse events that often accompany the treatment.
“The blood counts of patients should be analyzed for these biomarkers when making a decision about immunotherapy. This will dramatically increase the share of patients who will benefit from this type of therapy. At the same time, it makes it possible to directly move on to different methods in cases where immunotherapy won't work—without losing valuable time.” senior author Burkhard Becher of University of Zurich said.
- Krieg C, Nowicka M, Guglietta S, Schindler S, Hartmann FJ, Weber LM, Dummer R, Robinson MD, Levesque MP, Becher B. High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy. Nat Med 2018; 24(2):144–153.
The development of interferon-sensitive influenza vaccine strain
The influenza virus has evolved ways to inhibit interferon production in the host, which often leads to low immunogenicity of vaccine strains. A new study presented a recombinant influenza A virus with eight genes for interferon evasion having been disrupted.Citation1 This strain induced robust cellular and humoral responses and provided protection against viral challenge in mice and ferrets.
“With this approach, the safety and efficacy requirement of vaccines can potentially be achieved simultaneously. In traditional vaccine development, one is usually sacrificed for the other,” senior author Ren Sun of University of California in Los Angeles said.
- Du Y, Xin L, Shi Y, Zhang TH, Wu NC, Dai L, Gong D, Brar G, Shu S, Luo J, Reiley W, Tseng YW, Bai H, Wu TT, Wang J, Shu Y, Sun R. Genome-wide identification of interferon-sensitive mutations enables influenza vaccine design. Science 2018;359(6373):290–296.
Combination immunotherapy eliminated multiple cancer types in a preclinical study
Immune stimulation by the TLR9 ligand CpG oligonucleotide and agonistic anti-OX40 antibody showed promise in treating multiple solid tumor types. The locally administered immunotherapy resulted in the elimination of the tumor as well as distant metastases in mouse models of lymphoma, melanoma, breast and colon cancers.Citation1
“When we use these two agents together, we see the elimination of tumors all over the body,” senior author Ronald Levy of Stanford University said in a press release. “This approach bypasses the need to identify tumor-specific immune targets and doesn't require wholesale activation of the immune system or customization of a patient's immune cells.” Lymphoma patients are recruited for a clinical test of the method.
- Sagiv-Barfi I, Czerwinski DK, Levy S, Alam IS, Mayer AT, Gambhir SS, Levy R. Eradication of spontaneous malignancy by local immunotherapy. Sci Transl Med 2018;10(426).
Sanofi will refund unused Dengvaxia doses in Philippines and compensate vaccinees with adverse events
After the dengue vaccine Dengvaxia (Sanofi) was withdrawn from the Philippines due to the finding that the vaccine can exacerbate illness in people with no prior exposure to the virus, local authorities requested full refund of almost $70 million by the company. Sanofi agreed to pay back for unused doses (nearly $30 million) and promised to bear the costs of any adverse events or deaths related to the vaccine.
Dengvaxia's approval was suspended for a year in the Philippines. >700,000 schoolchildren had been immunized before the national campaign was discontinued.
Zika vaccine candidate fast-tracked by FDA
The US Food and Drug Administration has granted a fast-track designation to the Zika vaccine TAK-426 (Takeda). The purified, inactivated, aluminum-adjuvanted whole-virus vaccine entered a 240-subject Phase 1 trial in late 2017, and the designation means it is eligible for accelerated approval.
Zika, which causes congenital brain damage in children born to infected mothers, has declined significantly in incidence since the epidemic in 2015–6, so much so that WHO changed its classification from “public health emergency” to “long-term commitment.” The decrease in Zika incidence has made it difficult for vaccine developers to conduct large-scale clinical trials.
CMV vaccine fails late-stage trial in HSCT patients
THE CMV vaccine candidate ASP0113 (Astellas & Vical) has failed to meet primary and secondary endpoints in a Phase 3 trial involving hematopoietic stem cell transplant recipients. The vaccine did not improve overall survival, organ disease or time to first CMV detection.
ASP0113 is a bivalent DNA vaccine encoding CMV pp65 and gB antigens. It had previously failed in kidney transplant patients.
CMV is a herpesvirus which usually stays latent in the body but can develop into serious illness in people with impaired immune system. According to the US Centers for Disease Control and Prevention, more than half of Americans get infected by age 40.