Developing the sHIgM12 Human Antibody

Investigator: Larry Pease, Ph.D.

"The most exciting thing about Lymph 12 is that it's a human antibody. And Mayo's huge patient base and vast collection of serum samples allowed us to develop it expediently."
Larry Pease, Ph.D.

Dr. Pease developed a powerful human antibody from stored blood serum that can promote a curative, immune response against established malignant melanoma and block inflammatory lung disease that resembles asthma in experimental animal models.

The antibody is formally known as sHIgM12 -- Lymph12 for short. Developing a human antibody has significant advantages over antibodies produced from other species because the animal-origin marks the antibody for detection in human immune systems, causing an undesirable immune response. By contrast, Lymph 12 is a natural component of the human body that favors rapid, effective development of new immunotherapeutic agents.

In animal tests, Lymph12 has shown extraordinarily powerful health-giving effects when it binds to cells called dendritic cells. The effect boosts their survival, improves their ability to reach draining lymph cells and increases their ability to stimulate responses by T cells. T cells are the attack invading disease while dendritic cells identify and select which T cells are suited for attacking a given pathogen, and then mobilize them to attack.

Lymph 12 has newly-discovered, interesting, and important biologic effects when it binds to dendritic cells. In animal experiments Lymph 12 has been shown to enhance the ability of the dendritic cells to:

• Engulf, drink or otherwise take up antigens
• Travel to the lymph nodes
• Stimulate T cells

All three of these steps are key components of an effective immune response. The role of Lymph 12 is important because none of the steps are activated by the presence of a cancer tumor cell. Unfortunately, the body doesn't consider cancer tumor cells an infection, so this multi-step process is not stimulated by them. But if the laboratory results of Lymph 12 hold up in humans, physicians could be able to jumpstart the dendritic cells with Lymph 12, and "turn-on" the three-step immune response outlined above.

Dendritic cells can be manipulated to stimulate immune responses to destroy tumor cells.

It is important to learn how to therapeutically preserve dendritic cell function could be enlisted to boost the immune system to fight disease. In addition, Lymph 12 appears to increase the number of transplanted dendritic cells that travel to the lymph nodes. This is important because the lymph node is the site of interaction between dendritic cells and T cells in which the dendritic cells identify and mobilize the T cells best suited to attack the specific invader.

A key attribute of Lymph 12 for immunotherapy purposes is that it prompts dendritic cells to secrete communicating chemicals that drive TH1 immunity - the kind that fights cancer cells. The therapeutic ability to control this would be enormously helpful for cancer patients who need a boost to fight tumors. Treatment with the antibody can also block allergic responses leading to in inflammatory lung diseases, such as seen in allergic asthma. When Lymph 12 binds to dendritic cells, it increases their effectiveness in mobilizing T cells - highly activated T cells can go out and do their job and help the body kill cancer tumor cells