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Gene therapy research is gearing up in St. Luke's Medical Center

Dr. Robert G. Johnson delivered his talk entitled “A Cancer Gene therapy utilizing an Innovative Imaging Probe” last September 13, 2013 at the Angelo King Auditorium of St. Luke’s College of Medicine. The audience consisted mainly of interested doctors and students alike.

“An essential tenet of drug development... [is that] you make... a better drug”, Dr. Johnson said, referring to the rapid developments taking place in the field of cancer gene therapy. Cancer gene therapy is one of the newest possibilities explored in tumor treatment, recognizing the need for better forms of preventing the spread of malignant cells through various cytotoxic means.

In his talk, Dr. Johnson briefly explained the method used in delivering genes of interest into the cancer genes, using a vector containing the gene of interest whether RNA, DNA, Essential Viral Proteins Or Helper DNA. Transduction of the vector to the target cells allows incorporation of the gene of interest exclusively into the cancer cell genome, expressing proteins that counteract cancer cell function.

Some of the drugs that are currently in development, as stated by Dr. Johnson, are (1) Rexin-G, a retrovector that arrests cancer cell cycle in the G1 phase, (2)Reximmune C, also a retrovector drug that allows expression of GM-CSF inducing immune response by recruitment of host B-cells and dendritic cells into the tumor, and (3) Ganciclovir, an HSV/TK that arrests DNA replication via incorporation of guanine-like residues that terminate DNA elongation during replication.

Another interesting effect that is important in cancer treatment research, he said, is the so-called “bystander effect”. The bystander effect eliminates the need for entire tumor treatment. He said that gap junctions play a role in transferring the cytotoxic effects induced by a few vector-treated cells into the rest of the tumor, largely reducing the hazards of drug exposure to patients under treatment.

“The challenge is which patients are going to benefit in therapy”, he mused.

A new method of monitoring, Dr. Johnson continued, largely concerns the measuring of patient-response to administered Ganciclovir HSV/TK using [18F] FHBG, a novel probe that can monitor the expression of the thymidine kinase gene in tumor cells. “It’s well tolerated in normal humans and is rapidly cleared”, as Dr. Johnson describes the probe.

“Some patients were injected with Viral TK. Two days later, FHBG was administered, and, voila, the tumor lit up,” Dr. Johnson continued, citing studies done with the probe. “Which means that the tumor tissue had sufficient protein to allow the vector to bind, to transduce in the cell, and sufficient TK protein to be imaged.” FHBG, therefore, may be a useful tool in monitoring patient response to treatment. “Which in this case, the patient did respond,” he added.

In one of his slides, Dr. Johnson showed that in studies concerning mice there are “no clinical signs” and “no significant changes upon physical examination” after using the protocol. “In fact, the mice subjects gained weight”, he said.

The possibility of a clinical protocol using the novel probe is high in the St. Luke’s Medical Center as the hospital has a PET scanner, an important tool used to monitor FHBG in patients with hepatocellular carcinoma. A research protocol proposed by Dr. Johnson centers on the liver where a high distribution of the gene delivery system treatment is found.

“This is because the liver is more of [sic] the major reticuloendothelial organs in the body and that’s where you clear foreign proteins and microorganisms. So we’re going to use that in the clinical trial by looking at the tumors found there,” he said.

Dr. Filipinas Natividad, who has worked with Dr. Johnson in improving the protocol, said that the PET center has been in close talks with Dr. Johnson about meeting the requirements, particularly in resolving the ethical issues involved in the study, in performing this innovative study in the Medical Center.

“If this trial is going to be done here in our Medical Center, it would be a landmark study,” she said.