New Cancer Vaccine In Japan

[RandyW]

Advexin® is a Promising Vaccine for NSCLC and Esophageal Cancer

Researchers from Japan have reported that repeated intra-tumor injections of the vaccine Advexin (Ad5CMV-p53) produces clinical responses in patients with advanced non-small cell lung cancer. The details of this phase I study appeared in the April 10, 2006, issue of the Journal of Clinical Oncology .[1]

There have been many attempts to develop vaccine therapies for the treatment of cancer. However, at the present time there are no FDA approved vaccines for cancer therapy. Despite the difficulties of vaccine development, research continues in this field.

The p53 suppressor gene is of major focus in the evaluation of gene therapy since a significant portion of cancers have been shown to have a mutation (alteration) of this gene. The p53 gene, sometimes called the “cell suicide” gene, helps to keep normal cell replication under strict control. If there is a mutation in a cell’s DNA, or if a cell is infected with a virus, one action of the p53 gene is to stop further replication of this damaged cell and inhibit further progression of the mutation. This occurs by stopping the growth of the cell or causing the cell to kill itself (apoptosis). In cells that have a mutation within their p53 gene, there is no restraint on replication; this leads to uncontrolled growth of cancer cells.

Advexin® is a vaccine that is still in clinical trials. It is a functional p53 gene that is inserted into an adenovirus. Advexin is injected directly into tumor tissue. Researchers speculate that Advexin may have a direct cancer killing effect as well as enhance anticancer effects of treatment since cancer therapy often damages the DNA of cancer cells. A normal p53 should recognize this damage and halt replication or induce apoptosis of the cancer cell. A previous trial of this vaccine in the United States showed clinical responses to intra-tumor injection plus systemic Platinol® (cisplatin).[2]

Researchers from Japan recently conducted a clinical trial to evaluate the tolerability and effectiveness of repeat administrations of Advexin in patients with NSCLC. This trial included 15 patients with advanced or recurrent NSCLC that had a mutation within the p53 gene. Nine patients were treated with escalated doses of Advexin, and six were treated with Advexin plus Platinol.

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Thirteen patients were evaluable for responses to therapy: One patient achieved a partial regression of cancer; 10 patients had disease stabilization (three for more than 9 months), and two patients experienced disease progression.

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There were no side effects that resulted in a dose reduction.

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The most common side effect was fever that typically resolved itself within 24 hours.

The researchers concluded that repeat administration of Advexin appears well tolerated and effective in the treatment of advanced NSCLC in patients with a p53 mutation. Future trials further evaluating Advexin in the treatment of NSCLC are warranted.

According to a press release by Introgen Therapeutics, Inc., Advexin also appears promising as single-agent therapy in patients with inoperable refractory esophageal cancer.[3] This trial was also carried out in Japan and included 10 patients who were not eligible for surgery and had stopped responding to standard therapies. Patients were treated with Advexin as a single agent.

Advexin produced promising results:

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60% of patients experienced disease stabilization for more than one year.

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One patient remained alive and progression-free for nearly 4 years following treatment with Advexin.

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One patient who was not able to swallow upon entering the trial was able to swallow liquids and meals after two injections of Advexin.

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Advexin was well tolerated.

These researchers concluded that Advexin provides long-lasting anticancer responses while being well tolerated in patients with refractory, inoperable esophageal cancer. Advexin is still in the clinical trials processes and is not yet approved by the U.S. Food and Drug Administration (FDA).

Comments: Advexin has been in clinical trials for quite some time and appears to have some activity when injected directly into tumor tissue in association with chemotherapy. Whether or not these results will be enough to obtain FDA approval is uncertain.

References

[1]Fujiwara T, Tanaka N, Kanazawa S, et al. Multicenter Phase I Study of Repeated Intratumoral Delivery of Adenoviral p53 in Patients With Advanced Non–Small-Cell Lung Cancer. Journal of Clinical Oncology. 2006; 24: 1689-1699.

[2] Nemunaitis J, Swisher SG, Timmons T, et al. Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer. Journal of Clinical Oncology 2000;18:609-622.

[3] Introgen Therapeutics, Inc. Phase I/II Clinical Data Demonstrate Safety and Antitumor Activity of Introgen's ADVEXIN® in Patients With Advanced Esophageal Cancer. Available at: http://www.corporate-ir.net/ireye/ir_si ... _id=832621. Accessed March 2006.