新疫苗刺激结肠直肠癌症患者的免疫系统

生物谷

        英国的研究人员开发出可以刺激结肠直肠癌症患者的免疫系统，使其可以与癌细胞战斗的疫苗。

        在一项包含67名患者的临床试验中，诺丁汉大学的研究人员将这些疫苗施打于以手术去除肿瘤的患者，结果可以帮助百分之70的患者之免疫细胞制造。这些研究结果发表于11月15  日的Clinical  Cancer  Research中。

        研究作者Lindy  Durrant教授表示，这是第一支经过证实可以刺激TNFα的疫苗，这是一种可以非常有效地杀死癌细胞的免疫系统蛋白质。

        疫苗可以刺激患者的免疫反应，以产生可对抗感染的T  细胞，T  细胞又可以制造名为细胞激素的免疫系统蛋白质，而破坏癌细胞。

        这种疫苗内含的抗体称为105AD7，是从结肠直肠癌症转移至肝脏且存活了七年的患者身上复制的抗体。

        由于大多数的患者在肿瘤转移到肝脏后的一年内就会死亡，但是这名患者竟然活了七年以上。所以研究人员认为这种抗体可以帮助其它患者。

        105AD7的结构类似于CD55，这种蛋白质可以与糖分子结合，并且在结肠直肠癌细胞中过度表现，保护癌细胞免受身体免疫系统的攻击。暴露于免疫系统的细胞之CD55含量均偏低，但是许多肿瘤细胞的CD55表现量是增加的，包括百分之80的结肠直肠癌患者。

        经过临床研究后发现，这种疫苗可以让大约百分之70的患者生产了TNFα和  GM-CSF。但是这项试验并未设计来研究疫苗对于患者存活率的影响，所以还需要进一步研究。

英文原文：

New vaccine stimulates colorectal cancer patient's immune systems to fight cancerous cells

British researchers have developed a vaccine that stimulates colorectal cancer patients' immune systems to fight cancerous cells.

In a clinical trial of 67 patients, researchers at the University of Nottingham observed that when the vaccines were administered before and after surgery to remove cancerous tumors, they helped stimulated immune cell production in up to 70 percent of patients. These results are published in the November 15 issue of Clinical Cancer Research.

"This is the first vaccine shown to stimulate TNF-alpha ?an immune-system protein that is very effective at killing cancer cells," said Lindy Durrant, senior author of the study and professor of cancer immunotherapy at the university.

The vaccine works by stimulating the patients' immune response to generate infection-fighting white blood cells called T cells, which in turn produce immune system proteins called cytokines that destroy cancer cells. The antibody contained in the vaccine, called 105AD7, was cloned from a patient who survived seven years with liver metastases from colorectal cancer, Durrant explained.

"This is very unusual as most patients die within one year of getting liver metastases," she said. "I thought if this antibody had helped this patient, if we could clone it, it might help others."

105AD7 is structurally similar to CD55, a protein that attaches to sugar molecules and is overexpressed in colorectal cancer cells, protecting them from attack by the body's immune system. While low levels of CD55 occur in all cells exposed to the immune system, increased expression of the protein has been observed in multiple types of tumors, including up to 80 percent of colorectal cancers.

During the trial -- the largest to date looking at 105AD7 plus surgery -- 67 patients with colorectal cancer who were scheduled for surgery to remove their primary tumor were randomly assigned to receive either 100 micrograms of 105AD7 with a powder to help absorb the vaccine, 105AD7 along with BCG (a bacteria used to stimulate the immune system in cancer patients) during the first immunization and the powder in subsequent vaccinations, or no treatment.

The patients, who had varying degrees of disease, averaged age 66. Twenty-eight patients had colon cancer while in 39 patients the primary tumor was located in the rectum.

Patients were immunized before surgery on the day they were recruited for the study, and again two weeks later if surgery had not yet been performed. The vaccines were continued three, six and 12 weeks after surgery, and then at three monthly intervals up to a maximum of 24 months after surgery. Blood samples were collected from the patients during recruitment, at surgery, and at the time of the three-, six- and 12-week post-operative immunizations. Additional blood samples were acquired one month after each subsequent immunization.

Laboratory tests of the blood samples indicated that a T-cell response against the vaccine was recorded in the majority of patients. The responses tended to have two peaks: one following the start of the immunization schedule and another several months later, after additional immunizations. About 70 percent of patients produced both TNF-alpha and GM-CSF ?a protein that stimulates white blood cell production ?in response to both the vaccine and to CD55.

"The immune responses to both the vaccine and CD55 were measurable, adding support to the use of CD55 as a target in cancer treatment," Durrant said.

Nineteen of the patients died during the follow-up period. Durrant and colleagues noted that the trial was not designed to study the effect of the vaccines on survival.