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New brain cancer vaccine CDX-110 stops tumour growth in 70% of patients

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Monday, May 31, 2010, 11:30 This news item was posted in Biotech category and has 0 Comments so far.

A new vaccine targeting incurable form of brain cancer has been found arresting the growth of tumours in more than 70% of patients.

The experimental vaccines code-named CDX-110 is currently under early-stage studies in brain cancer patients.

An interim analysis of the clinical trial data showed that the vaccine CDX-110 prolong the lifetime of 70% patients afflicted with glioblastoma multiforme (GBM) – the most deadly form of brain cancer — without worsening their symptoms.

CDX-110 is an immunotherapy that targets the tumor specific molecule called EGFRvIII. CDX-110 is designed to activate the patient’s immune response against tumor cells specifically expressing the EGFRvIII mutation.

This protein is a variant of the epidermal growth factor receptor (EGFR), and is found in brain cancer causing cells.

Unlike EGFR, EGFRvIII is not present in normal tissues. This makes it a safer option as   it will enable the development of a tumor-specific therapy for cancer patients.

EGFRvIII has not been detected at a significant level in normal tissues, and it can directly lead to cancer through its well documented oncogenic properties that provide a constant growth signal to tumor cells which bear it.

Cells producing EGFRvIII have an enhanced capacity for unregulated growth.
Furthermore, EGFRvIII is a transforming oncogene that can directly contribute to the cancer cell growth.

While originally discovered in glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer, the expression of EGFRvIII has also been observed in various other cancers such as breast, ovarian, metastatic prostate, colorectal, and head & neck cancers.

CDX-110 has been studied in 40 patients with newly diagnosed GBM patients in an interim analysis of a study by the American Society for Clinical Oncology.

The study analysed the safety of CDX-110 when administered during a 12 month course of maintenance temozolomide chemotherapy and then continuing until disease progression.

Newly diagnosed patients received injections of CDX-110 along with radiation therapy and Merck & Co.’s Temodar until their tumor progressed.

All patients received the experimental treatment.

Normally, brain cancer progresses in about 50 percent of patients during that time period, according to experts.

Earlier studies have demonstrated a significant increase in the time to disease progression and overall survival relative to other drugs in use.

The therapy has been well tolerated and significant immune responses to EGFRvIII were generated.

The only frequently observed side effect was inflammation at the injection site.
Importantly, 21 out of 24 relapsed tumors that were biopsied or resected were found to no longer have significant EGFRvIII expression, suggesting a potent immune rejection of EGFRvIII expressing tumor cells.

CDX is currently being developed by Celldex Therapeutics in collaboration with Pfizer Inc.

Celldex’s primary focus is cancer therapy.

Apart from CDX, Celldex has three other programs currently in clinical development for treatment of multiple cancers.

CDX-011 is Celldex’ lead antibody-drug conjugate with potential for development with its Precision Targeted Immunotherapy Platform.

CDX-1307 and CDX-1401, use our APC Targeting Technology. A number of additional programs using the APC targeting and therapeutic antibody approaches are progressing towards clinical development.

What is glioblastoma multiforme (GBM)?

Glioma (cancer of the glial cells) is the most common type of malignant primary brain tumour (a tumour that originates in the brain).

Glioblastoma multiforme (GBM) is the most common and most malignant of the glial tumors.

Glioblastomas primarily affect adults, and they are located preferentially in the cerebral hemispheres.

Much less commonly, glioblastoma multiforme can affect the brainstem (especially in children) and the spinal cord.

Glioblastomas can be classified as primary or secondary. Primary glioblastoma multiforme accounts for the vast majority of cases (60%) in adults older than 50 years.

These tumors manifest without clinical or histopathologic evidence of a preexisting, less-malignant precursor lesion), presenting after a short clinical history, usually less than 3 months.

Secondary glioblastoma multiformes (40%) typically develop in younger patients of less than 45 years.

The time required for this progression varies considerably, ranging from less than 1 year to more than 10 years, with a mean interval of 4-5 years.

Patients treated with surgery, radiation therapy, and chemotherapy, have a median survival of approximately 12 months, with fewer than 25% of patients surviving up to 2 years and fewer than 10% of patients surviving up to 5 years.

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