# GPA33-Targeted Trimeric Immunotoxin Exhibits Enhanced Antitumor Activity in Human Colorectal Cancer Xenografts

## TL;DR

A new trimeric immunotoxin targeting GPA33 shows improved antitumor effects in human colorectal cancer models.

## Contribution

A novel trimeric immunotoxin combining GPA33 targeting and α-sarcin toxin is developed for enhanced colorectal cancer therapy.

## Key findings

- IMTXTriA33αS exhibits greater avidity and toxic load compared to conventional immunotoxins.
- The trimeric structure significantly improves in vitro and in vivo antitumor efficacy.
- The immunotoxin shows promise for overcoming limitations in solid tumor targeting and toxicity.

## Abstract

Immunotoxins are chimeric molecules with high potential as therapeutic candidates that combine antibody specificity to recognize and bind tumor-associated antigens and the cytotoxic potency of the enzymatic activity of a toxin, leading to the selective death of target cells. The use of immunotoxins as therapeutic tools remains limited by various issues, such as selecting the appropriate tumor-associated antigen (TAA), penetration difficulties in solid tumors, low renal clearance, and low toxic payload. For this purpose, in this work we have designed a novel trimeric immunotoxin (IMTXTriA33αS) against colorectal cancer, combining the scFv against GPA33 as a targeting domain and the fungal ribotoxin α-sarcin (αS) as the toxic fragment, linked by a trimerization domain (TIEXVIII). Our results demonstrate that IMTXTriA33αS has greater avidity and toxic load, showing a very significant increase in its in vitro and in vivo antitumor efficacy, due to its trimeric structure.