Pardoll and Allison reply:

In response to our commentary defining potential barriers to development of novel immunotherapy opportunities, Skipper and colleagues describe a unique cancer immunotherapy consortium developed by the Ludwig Institute for Cancer Research (LICR) and joined by the Cancer Research Institute (CRI). The LICR-CRI cancer vaccine collaborative (CVC) funds units in roughly 20 institutions. These units participate in a set of coordinated cancer vaccine clinical trials focused on vaccination with a limited number of tumor antigens identified at LICR and evaluates both the generation of antigen-specific immune responses as well as clinical outcomes. As director of both institutes, Dr. Old has marshaled their vast collective resources in a visionary manner to create a multi-institutional mini-Manhattan Project. CVC's funding base allows the organization to circumvent some of the regulatory and 'public-private partnership' barriers outlined in our commentary. However, the LICR-CRI CVC is arguably so unique, it represents the exception that proves the rule.

The projects being developed within the LICR-CRI CVC represent a small fraction of the tremendously promising opportunities provided by the past 10 years of accelerated molecular immunology and oncology research. If 10 such 'immunotherapy collaboratives' were similarly funded, with infrastructure to facilitate productive interactions among them and with the US FDA as well as the private sector, then a reasonable proportion of the crop could be harvested.

Where could such resources come from? Skipper and colleagues suggest that leading academic centers reallocate institutional resources to build translational infrastructures similar to that of the LICR-CRI CVC. Unfortunately, given the ever-increasing financial strains on the provision of health care within academic medical centers, it is unrealistic to expect resources of comparable scope to become available through individual institutions. Even the CVC's resources provide limited leverage to mobilize the immunologic agents currently languishing within biotechnology and pharmaceutical company portfolios. Congress now allocates the NCI $5 billion per year to mobilize the most effective anticancer effort possible. While still a tiny fraction of the current military budget, it is a resource that cannot be ignored and must be leveraged as effectively as possible. In addition, no serious therapeutic development can or should go on without the active participation of the FDA. While we applaud the unique structure and opportunities offered by the LICR-CRI CVC, and hope it will inspire the creation of analogous efforts, the key govern-mental institutions charged with protecting and promoting the health of Americans must be solidly on the playing field working with individual investigator groups at academic institutions and the corporate world alike to develop effective combinatorial therapies for human cancer therapy.