Personalized cancer vaccines show activity in two indications
The personalized neoantigen vaccine GRANITE (Gritstone bio) extended progression-free survival by 70%, compared to chemotherapy, to 12 months in high-risk microsatellite-stable colorectal cancer patients enrolled in a randomized, open-label Phase 2/3 trial. GRANITE regimen consists of a chimpanzee adenovirus (ChAd68)-vectored prime and a self-amplifying mRNA boost carrying tumor-specific neoepitopes identified by individual tumor sequencing, combined with checkpoint inhibitors.Citation1
Another personalized cancer vaccine, TG4050 (Transgene & NEC), was strongly immunogenic in a randomized Phase 1 trial involving HPV-negative head-and-neck cancer. All 16 treated patients remained in remission after a median follow-up of >18 months, compared to three relapsed subjects in a control group of 16 subjects treated with standard of care. TG4050 is based on the myvac technology, in which the tumor is sequenced, and the most suitable neoantigens are selected using artificial intelligence and delivered in a Modified Vaccinia Ankara (MVA) viral vector.
Therapeutic HPV vaccine was safe in an early-stage trial
The therapeutic HPV vaccine VTP-200 (Barinthus Bio) was well tolerated and led to some viral clearance in 108 women aged 25–55 years with persistent HPV infection and low-grade cervical lesions. The placebo-controlled, dose-escalation Phase 1/2 APOLLO trial reported a 60% clearance rate at the highest dosage level, compared to 30% in the placebo group. The other dosage cohorts showed no improvement.
VTP-200, a hexavalent vaccine targeting five HPV serotypes, is administered as a ChAdOx-vectored prime and MVA-vectored boost.
Progress with immune checkpoint inhibitor combination therapies of solid cancers
The LAG-3 agonist eftilagimod alpha (Immutep) with the PD-1 inhibitor pembrolizumab (Keytruda, Merck) induced a 27% overall response rate and 58% disease control rate as first-line treatment in 26 subjects with PD-L1-low, recurrent, or metastatic head-and-neck squamous cell carcinoma. These results from the TACTI-003 Phase 2 trial compare favorably to typical prognosis.
The off-the-shelf vaccine SLATE (Gritstone bio) with anti-PD-1 nivolumab (Opdivo) and anti-CTLA-4 ipilimumab (Yervoy, both BMS) was safe in 19 patients with advanced or metastatic solid tumors enrolled in a Phase 1/2 trial.Citation1 SLATE targets 20 frequent neoantigens shared across multiple cancer types.
Finally, the PD-1 inhibitor toripalimab (Junshi Biosciences), combined with the small-molecule inhibitor axitinib, was approved in China as first-line treatment for unresectable or metastatic renal cell carcinoma.
Covid-19 vaccines prevent long covid in adults
Both mRNA and viral-vectored COVID-19 vaccines reduce the risk of long Covid in adults by ~50%, two large studies involving 20 million Europeans showed.Citation2,Citation3 The results add to previous reports showing vaccination also prevents long Covid in children.Citation4
Long Covid is a set of symptoms that can develop following SARS-CoV-2 infection, including fatigue, shortness of breath, cardiovascular, and neurological problems.
30% response rate following interleukin-2 superagonist therapy in solid tumors
The IL-2 superagonist MDNA11 (Medicenna) induced four partial responses and three cases of stable disease in 14 patients with melanoma, pancreatic, and small bowel cancers. The Phase 1/2 ABILITY-1 trial reported good safety profile with no dose-limiting toxicities.
MDNA11 is an engineered superkine designed to stimulate intratumoral CD8+ and NK cells.
Long-term benefit induced by neoantigen vaccine in pancreatic cancer
50% three-year immunogenicity rate induced by the personalized vaccine autogene cevumeran (Genentech & BioNTech) combined with the PD-1 inhibitor atezolizumab (Roche) was reported from a Phase 1 trial involving 16 subjects with resected pancreatic ductal adenocarcinoma. Six patients remain disease-free.
Autogene cevumeran is a lipid-delivered mRNA vaccine encoding up to 20 tumor-specific neoantigens derived from bioinformatical analysis of deep-sequenced tumors obtained from each patient.
Promising results for oncolytic virotherapy of eye cancer
The oncolytic adenovirus VCN-01 (Theriva Biologics) was safe and demonstrated some antitumor activity without altering eye function in nine patients with refractory intraocular retinoblastoma.
VCN-01, which is administered in two intravitreal doses 2 weeks apart, is designed to replicate in tumor cells and turn them immunologically hot by destroying the surrounding stromal tissue.
CAR-T cell therapy of multiple myeloma approved in EU
The European Commission has approved the CAR-T cell regimen ciltacabtagene autoleucel (cilta-cel/Carvytki, Janssen) as ≥second-line treatment of relapsed and refractory multiple myeloma. The decision is based on the Phase 3 CARTITUDE-4 trial showing a 75% reduction in disease progression or death compared to standard of care.
Cilta-cel targets the B-cell maturation antigen, which is overexpressed in multiple myeloma.
Positive early data for a norovirus vaccine in lactating mothers
A bivalent oral norovirus vaccine (Vaxart) was safe and immunogenic in the Phase 1 VXA-NVV-108 trial enrolling 76 lactating mothers aged 18–43 years. The vaccine induced a 4-fold and 6-fold increase in antibodies targeting the GI.1 and GII.4 viral strains, respectively, in the high-dose group.
The vaccine is a recombinant oral pill vaccine. Currently, there is no licensed vaccine for norovirus, which is a significant concern for risk groups including children under the age of 5.
References
- Rappaport AR, Kyi C, Lane M, Hart MG, Johnson ML, Henick BS, Liao CY, Mahipal A, Shergill A, Spira AI. et al. 2024. A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results. Nat Med. 30(4):1013–2. doi: 10.1038/s41591-024-02851-9.
- Català M, Mercadé-Besora N, Kolde R, Trinh NTH, Roel E, Burn E, Rathod-Mistry T, Kostka K, Man WY, Delmestri A. et al. 2024. The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia. Lancet Respir Med. 12(3):225–36. doi: 10.1016/S2213-2600(23)00414-9.
- Trinh NT, Jödicke AM, Català M, Mercadé-Besora N, Hayati S, Lupattelli A, Prieto-Alhambra D, Nordeng HM. 2024. Effectiveness of COVID-19 vaccines to prevent long COVID: data from Norway. Lancet Respir Med. 12(5):33–4. doi: 10.1016/S2213-2600(24)00082-1.
- Yousaf AR, Mak J, Gwynn L, Bloodworth R, Rai R, Jeddy Z, LB L, Edwards L, Olsho LEW, Newes-Adeyi G et al. 2023. COVID-19 mRNA vaccination reduces the occurrence of post-COVID conditions in U.S. Children aged 5–17 years following omicron SARS-CoV-2 infection, July 2021–September 2022. Vol. 10, Open Forum Infect Dis; p. ofad500.2466.