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Hum Vaccin Immunother
Hum Vaccin Immunother
Human Vaccines & Immunotherapeutics
2164-5515
2164-554X
Taylor & Francis

39212628
10.1080/21645515.2024.2367397
2367397
Version of Record
Editorial
News, Policy, & Profiles
Human vaccines and immunotherapeutics: News May 2024
EDITORIAL
HUMAN VACCINES & IMMUNOTHERAPEUTICS
Ellis Ronald
Weiss Adam
Editor-in-Chief , Jerusalem, Israel
Taylor & Francis Group
rellis.hvi@gmail.com.
30 8 2024
2024
30 8 2024
20 1 2367397Integra14 6 2024
Integra14 6 2024
© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.
2024
The Author(s)
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
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pmcClinical progress with oncolytic virotherapies

The adenovirus-based virotherapeutic CAN-2409 (Candel Therapeutics) combined with immune checkpoint inhibition (ICI) increased median overall survival to 21 months in patients with advanced non-small cell lung cancer who had progressed following anti-PD-(L)1 immunotherapy. The standard-of-care chemotherapy leads to a ~ 12-month median survival in this population. CAN-2409 consists of non-replicative adenovirus designed to deliver the herpes simplex virus thymidine kinase into tumors, which converts valacyclovir (administered orally) into a toxic compound.

The replication-competent oncolytic HSV CAN-3110 (Candel Therapeutics) received the FDA’s Orphan-Drug designation for treatment of recurrent high-grade glioma. The regimen, which relies on the brain tumor-specific nestin promoter to express HSV virulence genes, proved safe and apparently increased survival in an early trial.

Another oncolytic adenovirus, VCN-01 (Theriva Biologics), combined with chemotherapy, received the Fast-Track designation from the US Food and Drug Administration (FDA) for treatment of metastatic pancreatic adenocarcinoma. VCN-01 is designed to replicate in tumor cells and turn them immunologically hot by destroying the surrounding stromal tissue.

Peptide vaccine induces high response rate in non-Hodgkin lymphoma

The off-the-shelf, microbial-derived peptide vaccine EO2463 (Enterome), combined with the immunomodulatory lenalidomide and rituximab, induced a 78% complete response rate in 9 patients with indolent non-Hodgkin lymphoma enrolled in the Phase 1/2 EONHL1–20/SIDNEY trial. The treatment was safe and induced cytotoxic T-cell responses specific for cancer-specific B-cell antigens.

EO2463 consists of peptides mimicking the B-cell markers CD20, CD22, CD37, and CD268, which are present in non-Hodgkin lymphoma.

>90% response rate for CAR-T cell therapy of AL amyloidosis

Twelve out of 13 patients with relapsed or refractory light-chain amyloidosis responded to the autologous CAR-T cell therapy NXC-201 (Immix Biopharma) targeting the B-cell maturation antigen (BCMA), with nine complete responses. The Phase 1/2 NEXICART-1 trial enrolled subjects with a median of four lines of prior treatment.

Light-chain amyloidosis is caused by abnormal B cells that produce amyloids consisting of dysfunctional antibody light chains.

PD-1 inhibitors bring survival benefit in multiple cancer indications

The anti-PD1-MAb pembrolizumab (Keytruda, Merck) combined with the immunoglobulin receptor LAIR2 fusion protein NC410 (NextCure) induced stable disease in 46% of 37 ICI-naïve microsatellite instability-low or stable colorectal and ovarian cancer patients.

Pembrolizumab with the oncolytic immunotherapy cretostimogene grenadenorepvec (CG Oncology) showed a 54% complete response rate and 100% progression-free survival rate, at the two-year mark, in 35 subjects with BCG-unresponsive, non-muscle-invasive bladder cancer engaged in the Phase 2 CORE-001 trial. Cretostimogene grenadenorepvec consists of tumor-specific adenovirus expressing the GM-CSF adjuvant, administered directly into the bladder.

First-line treatment with the PD-1 inhibitor camrelizumab (Elevar Therapeutics) and a small-molecule inhibitor induced a median overall survival of 24 months, compared to 15 months following standard-of-care therapy, in unresectable hepatocellular carcinoma. The randomized, open-label Phase 3 CARES-310 trial enrolled > 500 patients who had not received prior systemic therapy.

Intratumoral chemokine receptor inhibition was safe in early trial

The CCR8 inhibitor CHS-114 (Coherus) was safe in the dose-escalation, Phase 1 SRF114–101 trial involving 20 heavily pretreated subjects with advanced solid tumors.

CCR8 is a chemokine receptor expressed on tumor-resident Treg cells. CHS-114 is therefore designed to activate immunity in the tumor microenvironment.

KRAS vaccine was safe and immunogenic in solid cancers

The KRAS vaccine ELI-002 (Elicio Therapeutics) was well tolerated and induced specific T-cell responses in pancreatic and colorectal cancer patients as part of the Phase 1 AMPLIFY-7P trial.

ELI-002 is a CpG-adjuvanted vaccine targeting mutated KRAS protein, which is one of the most common tumor-associated neoantigens.

Bispecific antibody shows encouraging early-trial results

Twenty-five percent partial response rate and 50% stable-disease rate in 12 subjects with advanced solid tumors were reported from a dose-escalation Phase 1 trial investigating the PD-L1- and 4-1BB-targeting bispecific antibody ragistomig (I-Mab). The treatment, which is designed both to overcome PD-1-mediated inhibition and to directly stimulate T cells, had a manageable safety profile.

The HLA-G-targeting MAb TTX-080 (Tizona Therapeutics) combined with the EGFR inhibitor cetuximab (Erbitux, Merck) induced median progression-free survival rate of 24% in 48 subjects with advanced colorectal and head-and-neck cancers, with 30% and 60% overall response rates, respectively, in evaluable patients.

TTX-080, which inhibits the immune checkpoint HLA-G, is being tested in the open-label, dose-escalation Phase 1 trial in combination with cetuximab and pembrolizumab in a total of 240 subjects.

Chikungunya vaccine demonstrates long-term immunogenicity in adolescents

The chikungunya vaccine VLA1553 (Ixchiq, Valneva) induced 99% seroresponse rate after 180 days in > 200 adolescents aged 12–17 years. The randomized, double-blind, placebo-controlled Phase 3 VLA1553–321 trial reported no safety concerns.

VLA1553, approved by the FDA for adults in late 2023, is a single-dose, live attenuated vaccine against the mosquito-borne viral infection, which is a significant public health burden in tropical regions of the world.

Universal influenza vaccine shows promise in a preclinical study

A vaccine based on a mixture of hemagglutinin epitopes from diverse influenza strains protected animal models from both homo- and heterologous challenges.1 Vaccination induced antibodies targeting the conserved hemagglutinin stalk domain and in some cases improved binding to the head domain as well.

The influenza vaccine, which needs to be produced and administered annually based on analysis of circulating strains, typically offers only moderate protection.

Disclosure statement

No potential conflict of interest was reported by the author(s).
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Reference

1. Luo Z, Miranda HA, Burke KN, Spurrier MA, Berry M, Stover EL, Spreng RL, Waitt G, Soderblom EJ, Macintyre AN. et al. Vaccination with antigenically complex hemagglutinin mixtures confers broad protection from influenza disease. Sci Transl Med. 2024;16 (745 ):eadj4685. doi:10.1126/scitranslmed.adj4685.38691617
