Human vaccines and immunotherapeutics: News December 2023

Vaccination reduces the risk of long COVID in children

mRNA vaccination cut by about one-half the risk of developing two or more long Covid symptoms in children who had been infected by the SARS-CoV-2 Omicron strain.¹ The study, which looked at >600 subjects aged 5–17 years, most likely underestimated the rate of protection because it did not take into account the possibility that vaccinated children are less likely to contract infection in the first place.

Long Covid is a set of symptoms that can develop following COVID-19 infection, including fatigue, shortness of breath, cardiovascular and neurological problems.

Oncolytic virotherapies show promise in two cancer indications

75% complete response rate was induced by the oncolytic virotherapeutic cretostimogene grenadenorepvec (CG Oncology) in 116 patients with high-risk, BCG-unresponsive non-muscle invasive bladder cancer. Based on these results from the Phase 3 BOND-003 trial the US Food and Drug Administration (FDA) has granted the treatment its Breakthrough-Therapy designation. Cretostimogene grenadenorepvec is a recombinant adenovirus expressing the immune-stimulating cytokine GM-CSF.

Another oncolytic adenovirus, TILT-123 (igrelimogene litadenorepvec, TILT Biotherapeutics), in combination with tumor-infiltrating lymphocytes (TILs) isolated from resected tumors, led to disease control in six of 16 subjects with checkpoint-resistant stage IV metastatic melanoma, including one complete response. Five patients reported serious adverse events. The TILT-123 vector encodes TNF-alpha and IL-2, both of which are known to enhance TIL activity.

CAR-T cell therapy ameliorates autoimmune diseases

CD19-targeting CAR-T cell therapy resulted in significant clinical improvements in 15 patients with heavily pretreated, severe autoimmune diseases. In this Phase 1 trial, all participants could stop taking immunosuppressive drugs. A few subjects have remained in long-term remission despite reconstitution of CD19⁺ B cells in their blood. The indications included were systemic lupus erythematosus, idiopathic inflammatory myositis and systemic sclerosis.

The allogeneic CD7-specific CAR-T cell regimen WU-CART-007 (Wugen) was well tolerated at all dosage levels in a Phase 1/2 trial with relapsed or refractory T-cell acute lymphoblastic leukemia or lymphoma. At the dosage level selected for further development, >70% of patients went into remission.

Cellular immunotherapeutic fights brain metastases of breast cancer

Five out of seven breast cancer patients with central nervous system metastases responded to the off-the-shelf cellular immunotherapeutic Bria-IMT (BriaCell). Response was defined as ≥30% reduction in intracranial tumor tissue volume.

Bria-IMT consists of a breast cancer cell line with features of immune cells. It produces tumor-specific neoantigens, but the exact mechanism of this immunotherapy is not known.

Combination respiratory vaccine for RSV and hMPV is safe and immunogenic

A single dose of the VLP vaccine IVX-A12 (Icosavax) targeting respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) was safe and elicited strong antibody responses after one month in 240 adults 60–85 years old enrolled in a randomized, placebo-controlled Phase 2 trial. Immunogenicity was comparable with and without the MF59 adjuvant (Seqirus).

While the first RSV vaccine was approved recently, there is no vaccine available for preventing hMPV infection. Future trials are planned testing the VLP vaccine in a formulation targeting additional respiratory viruses, such as influenza and SARS-CoV-2.

Combination immunotherapy improves survival of colorectal cancer patients

First-line combination treatment with the PD-1 inhibitor nivolumab (Opdivo) and the CTLA-4 inhibitor ipilimumab (Yervoy, both BMS) improved progression-free survival, compared to chemotherapy, in >800 subjects with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer. Interim results from the Phase 3 CheckMate −8HW trial also reported no new safety concerns.

Colorectal cancer, which is the second most common cause of cancer-related death worldwide, is often diagnosed at a late stage, and patients face a poor prognosis.

Peptide conjugate vaccine is tested in prostate cancer

The synthetic therapeutic peptide vaccine TENDU (Ultimovacs) was safe and immunogenic in a dose-escalation Phase 1 trial involving 12 patients with relapsed prostate cancer. The vaccine was administered in four doses within six weeks, and the subjects were followed for six months after the last dose.

TENDU consists of prostate cancer-specific neoantigens conjugated to tetanus toxoid, which serves as an adjuvant. All eligible patients must have a record of prior tetanus vaccination and preexisting antibodies.

Chikungunya vaccine demonstrates durability

The recently approved chikungunya vaccine VLA-1553 (Ixchiq, Valneva) showed 97% immune persistence after two years in >300 adults enrolled into the Phase 3 VLA1553–303. Neutralizing antibody titers were robust irrespective of the subjects’ age.

VLA1553, approved by FDA 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.

Therapeutic antibody omalizumab can decrease severity of multiple food allergies

The FDA has granted Priority Review to the anti-IgE MAb omalizumab (Xolair, Roche) for amelioration of allergic reactions and prevention of anaphylaxis following accidental exposure to peanut, milk, egg and cashew allergens.

Interim analysis of the randomized, double-blind, placebo-controlled Phase 3 OUtMATCH trial data indicated that omalizumab significantly increased the amount of protein needed to cause allergic reaction to all four allergens in children and adolescents. The trial met both primary and secondary endpoints, but no actual rates have been disclosed.