Abalos Therapeutics has published two peer-reviewed preclinical studies providing new mechanistic evidence for its AdaptInnate immunotherapy approach, which uses tumor-adapted lymphocytic choriomeningitis virus (LCMV) to stimulate innate and adaptive immune responses against solid tumors.
The two studies, published in Viruses on September 11, 2026, examine how specific mutations in the viral glycoprotein can increase tumor tropism, alter systemic immune signaling, and enhance T-cell responses. The findings provide additional scientific support for the development of ABX-001, Abalos’ lead clinical candidate currently being evaluated in patients with advanced solid tumors.
Both studies focus on two mutations, I181M and R185W, located in GP1, the receptor-binding portion of the LCMV glycoprotein. The mutations were acquired as LCMV adapted to growth in cancer cells and appear to change how effectively the virus enters tumors and interacts with the immune system.
How Tumor Adaptation Changed LCMV
In the first study, titled Mutations at Positions 181 and 185 Within the LCMV GP Protein Increase Tumor Cell Infectivity, Limit Induction of Type I Interferon, and Accelerate T Cell Activation, researchers serially passaged wild-type LCMV-WE in the human H1975 lung cancer cell line.
After 29 passages, the virus had acquired the I181M and R185W mutations. The changes remained stable during subsequent passages, suggesting that they conferred a selective advantage in the tumor-cell environment.
Compared with wild-type LCMV-WE, the resulting LCMV-P52 strain showed increased infectivity and, in several settings, greater propagation in human cancer cells.
However, the mutations affected more than tumor-cell infection.
In mice, LCMV-P52 produced a lower systemic type I interferon response and showed accelerated expansion within CD169-positive macrophages. Viral propagation in the splenic marginal zone was associated with faster priming of virus-specific CD8-positive T cells.
Mechanistic experiments also showed markedly reduced infection of plasmacytoid dendritic cells, a major source of type I interferon during viral infection.
Despite stronger and earlier T-cell activation, the mutated virus was associated with less liver tissue injury than wild-type LCMV in the experimental models.
Together, the results suggest that the I181M and R185W mutations can alter both viral tropism and the balance between innate and adaptive immune activation.
Turning Tumors Into a More Immunogenic Environment
The second Viruses study, Lymphocytic Choriomeningitis Virus Bearing GPC Mutations for Enhanced Tumor Tropism and Strong Anti-Tumor Activity, examined how these glycoprotein modifications affect tumor infection and anti-tumor immunity.
Researchers found that LCMV-P52 preferentially replicated within tumors in vivo and showed improved penetration of tumor tissue compared with non-adapted virus. The treatment also increased recruitment of functional CD8-positive T cells into tumors and shifted the tumor microenvironment toward a more immunogenic state.
This feature may be particularly relevant for tumors with limited baseline immune-cell infiltration, one of the major barriers to successful cancer immunotherapy.
The preclinical studies further supported combining the approach with immune checkpoint blockade. In experimental models, LCMV-P52-induced immune activation created conditions that allowed greater activity from checkpoint inhibition, supporting further investigation of combinations with therapies targeting the PD-1 pathway.
This preclinical observation is also reflected in the clinical development strategy for ABX-001, which includes evaluation of the agent both alone and together with pembrolizumab, an anti-PD-1 antibody.
Jörg Vollmer, Chief Scientific Officer of Abalos Therapeutics, said:
“These studies deepen our understanding of how defined modifications to LCMV can increase tumor tropism and activate immune responses, two hallmarks of our AdaptInnate approach.”
He added that preferential viral replication within tumors following systemic administration, together with local T-cell responses, further supports the proposed mechanism of the platform.
A Different Approach to Cancer Virotherapy
Abalos’ strategy differs from conventional oncolytic virotherapy, in which viruses are generally designed to infect and directly destroy cancer cells through viral lysis.
LCMV is a non-cytopathic, or non-lytic, arenavirus. Abalos’ AdaptInnate approach is instead designed to allow the virus to infect, persist and replicate in tumor and antigen-presenting cells without directly destroying them.
The goal is to create sustained inflammation from within the tumor while simultaneously activating multiple components of the immune system, including tumor-directed T-cell responses.
Because the virus is administered systemically rather than directly into an individual tumor, the strategy is also intended to generate immune activity against metastatic lesions throughout the body.
Earlier Studies Supported Development of ABX-001
The new findings expand on research published in Cell Reports Medicine in 2025.
In that study, researchers used serial passage of LCMV through human and murine cancer cells to identify mutations capable of shifting viral tropism toward cancer.
An optimized LCMV containing the GP181M, GP185W and GP492I mutations showed accelerated propagation in multiple human tumor cells and tumor organoids while maintaining limited replication in healthy human cells.
A single intravenous administration produced anti-tumor activity in mouse cancer models with minimal replication in healthy tissues. In non-human primates, systemic administration triggered increases in virus-associated cytokines, chemokines and T-cell responses and was tolerated in preclinical safety testing.
Abalos has described these data as part of the preclinical foundation for its first AdaptInnate clinical candidate, ABX-001.
ABX-001 Moves Into Clinical Testing
ABX-001 is now being studied in the first-in-human Phase I/Ib trial NCT07231458 in adults with refractory or relapsed advanced solid tumors.
The open-label, non-randomized, multicenter study is designed to evaluate safety and tolerability, determine a recommended Phase 2 dose and assess preliminary anti-tumor activity.
The trial contains two parts:
- Part A: ABX-001 administered intravenously as monotherapy.
- Part B: ABX-001 followed by pembrolizumab beginning at Week 3, with pembrolizumab subsequently administered every three weeks.
The study’s primary outcomes include dose-limiting toxicities and treatment-emergent adverse events. Measures of early clinical activity include objective responses according to RECIST 1.1 and immune RECIST, as well as changes in target lesion size.
Abalos stated in its September 16 announcement that patient recruitment has been completed. The company expects initial Phase 1 data in 2027.
Gerben Moolhuizen, Chief Executive Officer of Abalos Therapeutics
“We are continuing to add important mechanistic evidence supporting our differentiated AdaptInnate approach and its potential to harness the immune-activating properties of arenaviruses to drive targeted and durable immune responses against tumors”
The upcoming clinical data will provide the first indication of whether the tumor tropism and immune activation observed across preclinical models can be translated into patients with advanced solid tumors.
Read further on OncoDaily: Can Oncolytic Viruses Make CAR-T-Cell Therapy More Adaptable in B-Cell Malignancies?
