CAR-T cell therapy induced responses in early trial with brain cancer
Fifty percent stable disease and two complete responses were induced by the CAR-T cell treatment MB-101 (Mustang Bio) in 65 heavily pretreated patients with recurrent and refractory, high-grade malignant glioma enrolled in a dose-escalation Phase 1 trial.Citation1 The regimen, which was tested with two routes of administration (intratumoral and intraventricular) and their combination, was well tolerated with no dose-limiting toxicities.
MB-101 targets the IL13Rα2 chain, thereby interfering with the anti-inflammatory functions of the IL13 pathway. IL13Rα2 is associated with poor prognosis by promoting migration and invasion of glioma cells.
Clinical progress of PD-1-targeting immune checkpoint inhibitors
The US Food and Drug Administration (FDA) has approved a PD-1 inhibitor, Tislelizumab (Tevimbra, BeiGene), that can be marketed as second-line treatment of advanced esophageal squamous cell carcinoma following chemotherapy. Data from the Phase 3 RATIONALE 302 trial indicate that tislelizumab decreases the risk of death by 30% compared to chemotherapy.
Nivolumab (Opdivo, BMS) in combination with chemotherapy has been approved for treatment of unresectable or metastatic urothelial carcinoma. Nivolumab reduced mortality risk by 22%, compared to chemotherapy alone, in the Phase 3 CHECKMATE-901 trial.
Finally, adding pembrolizumab (Keytruda, Merck) to chemoradiotherapy ‘significantly’ extended overall survival in subjects with early-stage cervical cancer, as reported by interim analysis of the Phase 3 KEYNOTE-A18 trial. No specific numbers have been disclosed. The regimen had previously been approved for late-stage cervical cancer.
Development of new Covid-19 vaccines and MAbs
The monoclonal antibody Pemgarda (Invivyd) has been approved by FDA for prophylactic use in immunocompromised individuals 12 y of age and older who are unlikely to mount immune responses following vaccination. Pemgarda, which targets the Spike surface protein of SARS-CoV-2, had been shown to neutralize the latest circulating strain JN.1.
The intranasal vaccine Avacc 10 (Intravacc) was safe and immunogenic as a booster dose in a randomized, double-blinded, placebo-controlled, dose-escalation Phase 1 trial involving 36 healthy adults. The vaccine, which is administered in two doses 3 weeks apart, consists of the antigen presented on outer membrane vesicles, themselves having adjuvant properties.
Parkinson’s disease vaccine shows signs of activity in an early trial
The Parkinson’s disease vaccine UB-312 (Vaxxinity) induced 20% decreased levels of pathological alpha-synuclein in the cerebrospinal fluid and some improvement in disease manifestations. The elicited antibodies also showed preferential binding to aggregated form of alpha-synuclein with almost no binding to the monomeric form.
The randomized, double-blind, placebo-controlled dose-escalation Phase 1 trial enrolled 20 Parkinson’s disease patients.
HeplisavB vaccine protects non-responders living with HIV
Three doses of the CpG-adjuvanted hepatitis B vaccine HepBCpG (Heplisav, Dynavax) achieved 99% protection in HIV patients who had not responded effectively to other hepatitis B vaccines. The randomized, multicenter, dose-escalation trial enrolled >500 HIV subjects undergoing antiretroviral therapy.
No safety concerns were reported, with most of the frequent adverse events being pain and fatigue.
Reference
- Brown CE, Hibbard JC, Alizadeh D, Blanchard MS, Natri HM, Wang D, Ostberg JR, Aguilar B, Wagner JR, Paul JA. et al. Locoregional delivery of IL-13Ralpha2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial. Nat Med. 2024. doi:10.1038/s41591-024-02875-1.