T cell cancers are often fatal, necessitating the generation of novel therapies. Targeting TRBC1 can kill T cell cancers while preserving sufficient healthy T cells to maintain immunity. However, the first-in-human clinical trial of anti-TRBC1 CAR T cells reported a low response rate and unexplained loss of anti-TRBC1 CAR T cells. Our study shows how the CAR T cells are lost due to killing by the patient’s normal T cells. We further show that the generation of TRBC1-targeting ADCs bypasses this limitation and may produce superior responses in patients with T cell cancers.

The development of antibodies for radiopharmaceutical therapy continues apace, with recent progress in engineered antibody formats and fusion proteins adding versatility to treatment approaches. Combination therapies are likely to provide the greatest efficacy, and prospects for combining radioimmunotherapy with modalities including external beam therapy and immunotherapies will be described. Clinical examples include targeting CD25 and CD38 in hematologic malignancies and CEA in colorectal and other adenocarcinomas.

Treating cancer requires balancing cytotoxicity, immune activation, and safety to eradicate malignant cells while sparing healthy tissue. Nanofitin-based drug conjugates offer a powerful solution by combining antibody-like high-affinity and specificity with the deep tumor penetration of small scaffolds. Their rapid systemic clearance minimizes off-target toxicity while ensuring efficient delivery of potent payloads such as MMAE. In preclinical models, weekly dosing of an MMAE-Nanofitin conjugate achieved complete tumor growth inhibition. This approach overcomes diffusion and resistance barriers by reaching tumor cells beyond vascularized regions, paving the way for next-generation targeted cancer therapeutics.

Achieving specificity and efficacy remain key challenges in immuno-oncology. We have developed a bispecific antibody-drug conjugate (ADC), integrating a tumor targeting arm with a functional arm that enhances immune engagement by a novel mechanism. This strategy enables selective payload delivery while amplifying the immune response in the tumor microenvironment. Preclinical studies demonstrate potent in vitro and in vivo activity.

Ragistomig (ABL503/TJ-L14B) is a bispecific antibody combining PD-L1 checkpoint pathway with 4-1BB agonistic activity to overcome the current limitation of PD-(L)1 therapy and 4-1BB related toxicity. ABL503 is full length anti-PD-L1 mAb (Fc-silenced human IgG1) fused with scFv of anti-4-1BB engaging mAb. Givastomig (ABL111/TJ033721) is a bispecific antibody designed to target tumors with a wide range of Claudin 18.2 (CLDN18.2) expression and engage 4-1BB through a unique conditional activation mechanism at the tumor sites to avoid systemic toxicities.

TA/CD3 bispecific antibody is a potent approach in cancer treatment, but its efficacy is limited to tumors with less T cell infiltration. Dual-Ig binds to both CD3 and CD137 in the same Fab non-simultaneously, providing Signal 1 and Signal 2 to overcome this limitation while preventing off-target killing of TA-negative cells. We present the mechanism underlying this non-simultaneously binding and demonstrate advantages over conventional bispecific antibodies.

We report a novel fusion protein, V5, for cancer immunotherapy. V5 contains a structure-guided, enhanced PD-1 ectodomain and a CD80 domain. The synergy of PD-1 blockade and T cell activation through CD80 led to persistent inhibition of various tumors in animal models, including colorectal, liver, pancreatic, and cholangiocarcinoma cancers, regardless of PD-L1 expression or resistance to conventional PD-1 blockade. V5 treatment induced effective immune memory. V5 also activates tumor-specific T cells via APCs and PD-L2 signaling. Preclinical studies in cynomolgus monkeys showed a promising safety profile, supporting V5 in human studies.

TCRm represent a promising modality for tumor-therapeutics. We have developed a robust TCRm discovery pipeline that enabled identification of the CTSG peptide–HLA-A*02 complex from AML blasts, leading to the clinical candidate CBX250 (in collaboration with Crossbow Therapeutics). CBX250 demonstrates potent in vitro and in vivo efficacy without detectable cross-reactivity, and US Phase I trials are ongoing. A first-in-class TCRm×CD3 targeting CCNB1 is also in IND-enabling studies to benefit more patients.

Tumors are very heterogenous and include immunosuppressive cell types, limiting the ability of current therapies to target all cells in the tumor with high potency. TROCEPT is a novel immuno-virotherapy that only targets cancer cells, and turns them into drug factories. We have used this technology to deliver a novel universal bispecific T cell engager, that can target all cancer cells, only inside the tumor.

CD3 T cell engagers activate T cells through Signal 1, but solid tumors generally lack the costimulatory signals required for full activation, potentially leading to anergy and reduced efficacy. Tumor-targeted CD28 bispecific antibodies that strictly depend on concurrent Signal 1 for costimulatory activity represent a key advancement in immunotherapy. Adding targeted costimulation enhances cytokine production, proliferation, survival, restores activity in restimulation settings, and drives stronger anti-tumor responses in preclinical models.

PD-1 and PD-L1 blocking antibodies have revolutionized immunotherapy of immune-infiltrated cancers through their capacity to revive, amplify and sustain T cell responses. Unfortunately, thousands of subsequent trials have shown that these drugs cannot overcome the multifactorial stromal barriers that mediate T cell exclusion and anergy in "cold" cancers. We show that PD-L1/PD-L2 dual-specific antibodies can combine complete PD-1 blockade with cytotoxic depletion of immune suppressive stroma to overcome cold cancers.

Epsilogen was founded to develop therapeutic IgE antibodies. Through acquisition of TigaTx in March 2025, Epsilogen is now also developing therapeutic IgA. Epsilogen's lead antibody, MOv18 IgE, targets folate receptor alpha and has completed a phase 1 clinical trial. It is currently in a phase Ib trial treating platinum-resistant ovarian cancer patients. Epsilogen also has IgE and IgA antibodies in pre-clinical studies and it has a number of proprietary platforms including bispecific IgE and hybrid antibodies that combine IgE or IgA with IgG functionality.