Immunovative Therapies' subsidiary ImmunoCare has reported the start of a Phase IIb study of CryoVax, a next-generation immunotherapy cancer vaccine product, for patients with chemotherapy-refractory (third line) metastatic colorectal cancer (mCRC).

The trial is being conducted by Banner MD Anderson Medical Center, in Phoenix, Arizona, which is partnered with University of Texas MD Anderson Cancer Center in Houston, Texas.

Recruitment in the trial is underway, and the first volunteers have received their initial vaccine doses.

Patient enrolment is expected to be completed by the end of July 2017.

"The CryoVax vaccine regimen has a unique mechanism of action and shows promise as a next-generation immunotherapy."

CryoVax is a next-generation immunotherapy intended to provide immune-mediated tumour killing effects for the remaining 85% of mCRC patients that fail to respond to checkpoint inhibition immunotherapy.

The CryoVax next generation immunotherapy regimen creates 'hot' tumours in patients and then blocks checkpoint molecule expression.   

Patients are first immunised against patented bioengineered immune cells called AlloStim, which are derived from healthy, intentionally mis-matched, donor cells. 

A vaccine is then created within the body, which customises the immune response to the patient’s own tumour.

Vaccines have a source of tumour antigens and an adjuvant to modulate the immune response.

The tumour antigens for the CryoVax vaccine are derived from the release of the inner contents of tumours (heat shock proteins) killed by extreme cold, a technique called cryoablation.

Intratumoral injection of AlloStim cells into the microenvironment of the cryoablation lesion containing dead tumour cells serves as an adjuvant, which creates an in-situ, personalised, anti-cancer vaccine.

Subsequent IV infusions of the AlloStim cells cause the movement of immune cells from the circulation into the tumour lesions. This movement of immune cells create hot tumours.

The highly inflammatory conditions created by the subsequent rejection of the mis-matched AlloStim cells serves to naturally down-regulate checkpoint molecules on tumour cells.

This combination of hot tumours and down-regulation of checkpoint molecules is a formula known to enable immune-mediate tumour killing of mCRC tumours.

CryoVax inventor and Immunovative Therapies CEO Dr Michael Har-Noy said: “Anti-tumour vaccines have had difficulties in translating into effective therapies in the clinic and mCRC has been particularly resistant to immunotherapy.

“The CryoVax vaccine regimen has a unique mechanism of action and shows promise as a next-generation immunotherapy.

“We will be studying various AlloStim dosing frequencies and closely monitoring the interaction of host immune cells with the tumour cells in each of the cohorts of this clinical trial. This information should serve to determine if this customised in-situ vaccine approach will benefit mCRC patients.”

Patients enrolled in the study will be divided into six groups and receive different dosing frequency schedules of AlloStim, with all subjects receiving cryoablation of a selected tumour lesion followed by an intra-tumoural injection of AlloStim to create a customised in-situ vaccine.