Investigating immunocytokines

Kymab partners with industry expert for more efficacious, tolerable therapies

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CAMBRIDGE, U.K.—In the hopes of using its proprietary platform to develop new cancer therapeutic options, Kymab has announced a collaboration with Dr. Stephen Gillies, a leader in cancer immunotherapy who has invented promising immunocytokine platforms. Gillies is the founder and CEO of Provenance Biopharmaceuticals Corp. and is also on the board of directors for Cambridge, Mass.-based Galenea Corp.
“I’m delighted to work with Kymab on development of novel treatments, work that promises to produce improved products for drug development in cancer. The program hits the ‘sweet spot’ of our joint expertise and will be used to develop new and transformational drugs in this fast-moving field,” said Gillies.
Kymab and Gillies will work together to develop new immunocytokine-based drugs that could exploit the synergistic potential of combining antibodies directed against immuno-oncology drug targets with the antitumor activity of certain cytokine molecules. Steve Arkinstall, chief scientific officer of Kymab, says the company has licensed Gillies’ immunocytokine intellectual property “as it relates to specific oncological drug targets.” Kymab will be responsible for all experimental work while Gillies will act in an advisory role for the project’s scientific and strategic direction. The collaboration will focus on targets that could have potential against several types of cancer.
“This new collaboration with one of the leading figures in immunocytokine research offers an exciting opportunity to develop new anticancer drug candidates,” Arkinstall commented. “Our world-beating antibody discovery technology will enable us to develop novel immuno-oncology drug candidates through leveraging the synergy of antibodies targeting cancer cells fused to selected cytokines localizing them to the tumor microenvironment. This in essence will give a ‘double-hit’ on cancer cells.”
Cytokines are small proteins that play important roles in cell signaling. They affect the behavior of immune cells, and several diseases feature cytokine malfunction, including infection, inflammatory diseases and cancer. Some cytokines demonstrate antitumor activity, but as is the case with a number of chemotherapeutic drugs, their therapeutic potential is hampered by their toxicity. As explained on Provenance’s website, Gillies’ approach uses a whole antibody format, in which a cytokine is genetically fused to the end of an antibody-heavy chain.
“When the antibody structure forms with the pairing of two heavy chains and two light chains, the immunocytokine molecule consists of a normal antibody structure with two antigen binding arms (termed Fabs) in the front, capable of binding two tumor target molecules on a cell surface. Once the immunocytokine binds to a tumor cell, it displays two cytokine molecules extending out from the cell that can be engaged by local immune cells adjacent to the tumor,” as noted on the website.
The effect this has depends on both the cytokine that is used and the type of immune cell, as “In some cases, the effect is similar to a bi-specific antibody when the cytokine acts as a trigger for an immune effector cell leading to direct tumor lysis, while in other cases it results in immune cell activation and proliferation of tumor-specific T cells that indirectly kill the tumor cells through their own recognition molecules (T cell receptors).”
“The benefits of immunocytokine drugs is that they are able to leverage the well-known anticancer therapeutic activity of some cytokines (e.g. IL-2, IL-12) while at the same time, minimizing the toxic side effects of these cytokines through targeting their activity specifically to the tumor micro-environment,” Arkinstall explains. “It is believed that high therapeutic benefit may be achieved at significantly lower doses than is achieved with approved cytokine treatment regimens.”
For its part, Kymab’s Kymouse technology can rapidly generate a range of fully human antibodies, offering high-affinity, candidate-quality molecules that require no further lead optimization since the molecules “are already optimized in vivo for affinity and biophysical properties,” the company website asserts.
“Our search for new treatments drives us to seek the best opportunities to move research forward towards drug development,” Dr. Christian Grøndahl, outgoing CEO of Kymab, said in a press release. “This is a biology-based, genome-driven, rational program that will use the power of our understanding of the immune system’s ability to combat cancer and will feed new and exciting products into our pipeline.”
“We are convinced that immunocytokine drugs, such as those emerging from our collaboration with Dr. Gillies, have the potential to be an important part of a new and varied armory of immuno-oncology-based treatments for cancer,” Arkinstall adds.

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