In one cancer therapy, two halves are safer than a whole
Splitting immunotoxins in half could increase their specificity toward cancers, study suggests

Date:
August 24, 2020
Source:
Ohio State University
Summary:
Splitting one type of cancer drug in half and delivering the
pieces separately to cancer cells could reduce life-threatening
side effects and protect healthy, non-cancerous cells, a new
study suggests.



FULL STORY ========================================================================== Splitting one type of cancer drug in half and delivering the pieces
separately to cancer cells could reduce life-threatening side effects
and protect healthy, non-cancerous cells, a new study suggests.


==========================================================================
The study, published today in the Proceedings of the National Academy
of Sciences, suggests that splitting immunotoxins into two inactive and
benign parts may set the stage for future, targeted treatments of cancers.

Immunotoxins combine an immune substance with a toxin. The immune
substance attaches to cancer cells, allowing the toxin to enter the
cancer cell and kill it without harming nearby healthy cells.

The research was designed as a proof-of-concept study, but the researchers found that the functional toxin can be reconstructed in cancer cells in
both laboratory cell cultures and in mice.

The search for a cancer cure has led to a number of treatments that
destroy cancer cells, but also destroy healthy, non-cancerous cells. That destruction often causes life-threatening side effects.

"The problem is not to kill the healthy cells," said Dmitri Kudryashov,
an associate chemistry professor at The Ohio State University and senior
author of the study. "What is difficult is to kill only the cancer cells
and nothing else." And while some cancer treatments have been successful
at targeting cancer cells, few have been able to do so without also
affecting healthy cells.



==========================================================================
The key to split immunotoxins is that only cancer cells will receive both
parts of the split toxin, said Elena Kudryashova, a co-senior author on
the study and a research scientist at Ohio State.

"We have confirmed that when separated, the parts of the split toxin
do not harm cells. But when they recombine into the original toxin,
the treatment destroys the cancer.

"But to achieve that, both parts must enter cancer cells," Kudryashova
said.

"What we have achieved so far is the reconstruction of the fully
functional toxin upon specific delivery of one part of the split
immunotoxin to the cells expressing the other part. The specific delivery
of this other part in sufficient quantity is yet to be achieved and is
being pursued in the laboratory." Essentially, when the toxin protein
is split and goes into the human body as a cancer treatment, it can't
cause harm to healthy cells. But if biochemists can find a way to get
both pieces of the protein to enter a cancer cell, the two pieces of
toxin can then destroy the cancer.

Other Ohio State researchers who worked on this study are a lead author,
Vedud Purde, and David Heisler and Reena Shakya.

This work was funded by the National Cancer Institute and a Pelotonia
Idea Grant.


========================================================================== Story Source: Materials provided by Ohio_State_University. Original
written by Laura Arenschield. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Vedud Purde, Elena Kudryashova, David B. Heisler, Reena Shakya,
Dmitri S.

Kudryashov. Intein-mediated cytoplasmic reconstitution of a split
toxin enables selective cell ablation in mixed populations and
tumor xenografts. Proceedings of the National Academy of Sciences,
2020; 202006603 DOI: 10.1073/pnas.2006603117 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200824160248.htm

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