Bladder cancer vaccine shows promise, says Celldex

A potential to new prevent and treat bladder cancer developed by Celldex Therapeutics shows promise.

The vaccine under development code-named CDX-1307 uses a new APC Targeting Technology. The technology utilizes fully human monoclonal antibodies to directly target specialized types of immune system cells, known as antigen presenting cells.

Celldex is currently developing CDX-1307 for the treatment of epithelial tumors such as colorectal, pancreatic, bladder, ovarian and breast cancers.

CDX-1307 is a cancer vaccine designed to activate the patient’s immune system against the beta chain of human chorionic gonadotropin. Known as hCG-beta, chorionic gonadotropin is an antigen often found in epithelial tumors including bladder cancer.

hCG-beta appears to directly facilitate cancer progression. The presence of hCG-beta in these cancers also leads to a poor clinical outcome, suggesting that this molecule may contribute to tumor growth.

The new vaccine CDX-1307 specifically targets the hCG-beta tumor antigen activity.

The bladder cancer vaccine induces robust immune responses against the antigen-expressing cancer cells.

Celldex plans a midstage clinical study with the bladder cancer vaccine candidate CDX-1307 in patients with newly diagnosed muscle-invasive bladder cancers that express hCG-beta.

Early trials (Phase 1) using the vaccine has been shown to generate a robust immune response against cancer cells expressing hCG-beta.

The Phase 2 study will enroll approximately 60 patients, with newly diagnosed hCG-beta expressing muscle-invasive bladder cancer who have not previously received any chemotherapy for their disease.

These chemo-naive patients will be most likely to have intact immune systems that are best able to generate a potent anti-tumor response, Celldex hopes.

Following screening with an hCG-beta diagnostic assay, patients will be randomized to receive neoadjuvant therapy with either CDX-1307 and standard of care chemotherapy (gemcitabine and cisplatinum) or standard of care alone, and will then undergo bladder resection.

Following bladder resection, patients administered neoadjuvant therapy will also receive adjuvant CDX-1307 vaccine for up to one year.

“Bladder cancer is an understudied disease with a real need for new therapies and hCG-beta is an important molecule in tumor biology that prevents tumor cell death,” said Professor Ray Iles, Middlesex University, London.

Newly diagnosed bladder cancer is an immunologically sensitive disease.

70,980 new cases of bladder cancer and 14,330 deaths from bladder cancer occurred in the United States in 2009, according to the American Cancer Society estimates.

The prognosis and treatment for patients diagnosed with bladder cancer is largely dependent on stage, with more advanced tumors carrying an increased probability of recurrence.

For patients with muscle-invasive disease undergoing radical surgery called cystectomy, 5-year recurrence-free survival has been reported to be in the range of 50-89%.

However, the subset of bladder cancer patients with hCG-beta expressing cancers (21-47%) fare much worse.

One study has indicated a median survival of just four months for Stage T3 bladder cancer patients expressing hCG-beta, compared to twenty-three months for those who did not express the antigen.

As hCG-beta appears to directly facilitate cancer progression through a number of mechanisms, an approach targeting hCG-beta in the treatment of bladder cancers may be a particularly effective strategy.

Celldex Therapeutics is the first antibody-based combination immunotherapy company.