Monash University researchers alongside key partner Halozyme Therapeutics have reported findings in support of shifting the way anti-cancer immunotherapy is administered from intravenous administration to subcutaneous administration in combination with recombinant hyaluronidase. This approach makes it less complex and painful for the patient, and may improve the treatment outcome for some medicines.
The study published in Cancer Immunology Research, addresses a current challenge that is that monoclonal antibody (mAb) immunotherapies typically require high doses/volumes to be effective and as a result are infused intravenously. In contrast, subcutaneous administration, where an injection is given under the skin, is an increasingly patient-preferred alternative as it is more convenient and less painful. However, this method is often not possible due to the high volume required to be administered.
To counter this, Halozyme Therapeutics developed a recombinant version of an enzyme called hyaluronidase. When co-administered in a subcutaneous injection, hyaluronidase transiently but almost immediately, breaks down one of the structural components of the space below the skin (hyaluronan) that restricts the subcutaneous injection of large volumes, thereby making an intravenous to subcutaneous transition possible.
Co-lead authors of the study, Professor Chris Porter, and Dr Orlagh Feeney from the Monash Institute of Pharmaceutical Sciences (MIPS), said that hyaluronidase has been used to facilitate subcutaneous injection for some time, but what has not been described before is whether administering with hyaluronidase might actually make therapy better rather than just more convenient.
"We show here, for the first time, that for some treatments that help the immune system fight cancer, when they are co-administered subcutaneously with hyaluronidase, they are indeed more effective and hyaluronidase is able to 'boost' the benefit of subcutaneous administration," Professor Porter said.
Co-lead author of the study, Dr Gracia Gracia, from the Monash Institute of Pharmaceutical Sciences (MIPS), said that this approach (subcutaneous injection with hyaluronidase) helps treatments to reach the lymphatic system, where immune responses are generated.
"Because the lymphatic system plays an important role in certain cancers—particularly those involving tumor-draining lymph nodes—delivering treatment directly to this system may be a promising therapeutic approach."
Co-author, Dr David Kang, Director of Drug Delivery and Innovation at Halozyme Therapeutics, said that "This study is the culmination of a long collaboration with MIPS to examine how co-administration with hyaluronidase might improve access to the lymphatic system after subcutaneous administration compared with intravenous administration. These findings provide additional rationale for adopting this approach for therapeutics that act at tumour‑draining lymph nodes, as many anticancer immunotherapies do. Transitioning from intravenous to subcutaneous administration not only improves convenience but also reduces patient discomfort."
The full study tilted Removal of interstitial hyaluronan facilitates subcutaneous
administration and lymphatic delivery of anti-ctla4 and improves antitumour efficacy can be found here.
