2004A0151 - Cytokine Therapy of Experimental Tumors - William E. Carson III - Pain Code = 4E

Since 1998 the goal of the experiments has been to determine the role of specific cellular proteins that mediate the response to cancer therapies.

The protocol falls into the "E" category as "due to the metastatic nature of melanoma cells lines, it is possible death may occur in some animals...Thus, although tumors may not reach the maximum size (1.5 cm in diameter) undetectable metastases could potentially migrate to internal sites, resulting in death prior to the 6 week time point."

200040151 was approved to use 4,363 mice from a variety of strains and breeding programs.

The initial protocol 98A0114 used 3,000 mice.

In 1998, the PI writes the "C57BL/6 mouse strain develops spontaneous melanoma tumors, cells from which can be cultured and injected in syngeneic (related) mice and will establish into new melanoma tumors."

In 2001, a new cell line is acquired and additional mice are requested for use. This new cell line is" highly metastatic, grows quickly in these mice (new strain BALB/c), and is resistant to numerous chemotherapeutics. Therefore, the efficacy and mechanism of action of our novel anti-cancer therapy can be examined in a controlled manner."

The PI begins attempts to "identify optimal dosing schedules."

Another amendment is approved to "add a surgical procedure in these tumor bearing mice to determine susceptibility to sepsis in the setting of treatments and malignant disease."

"The endpoint for this study will be when mice exhibit the signs of systemic sepsis (recognized by decreased activity, the animals fail to congregate for warmth, their coats are disheveled, and they exhibit piloerection-hair standing on end). Mice in this model exhibit a period of marked decrease in activity and at this point they are euthanized. Death is not the specific endpoint of this trial although there may be deaths from this experiment."

In 2002 additional mice and a variety of strains of mice are approved. Many of the strains "lack/have a defect in a specific type of immune cell. The characteristic may make them more susceptible to viral and bacterial infection."

So while death as an endpoint is not an objective some mice will die prior to reaching the early removal criteria. And of course, all mice are killed at the end of the experimental cycle.

2006A0210 is the new protocol for the same experiments, with variations, that have been conducted since 1998.