identified the pathway by which growth factors enter cells and established a mechanism that helped explain down-regulation of receptors and the loss of growth factor responsiveness. Following the identification of the EGF receptor by Stanley Cohen, Pastan and colleagues made several seminal advances that identified the EGF receptor as a proto-oncogene. Besides being one of the first 3 laboratories to obtain the DNA sequence of the EGF receptor, they showed that the EGF receptor gene was amplified, rearranged and over-expressed in many cancer cells including squamous cell carcinomas, and with Doug Lowy showed that over-expression of the EGF receptor in the presence of EGF is sufficient to transform normal 3T3 cells and therefore is a proto-oncogene. Altogether these studies provided much of the framework that ultimately led to the use of antibodies targeted to the EGF receptor as a cancer therapy. Pastan is currently developing a new therapy for cancer by making fusion proteins composed of the Fv portion of monoclonal antibodies directed at receptor proteins on cancer cells fused to a genetically modified form of a powerful bacterial toxin, Pseudomonas exotoxin A. Three of these genetically engineered proteins, which he named recombinant immunotoxins (RITs), are being tested in humans with various forms of cancer. One of these, HA22 or Moxetumomab pasudotox (Moxe), targets CD22 on B cell malignancies; it has produced many complete and durable remissions in chemotherapy resistant Hairy cell leukemia and is now in a phase 3 trial to gain FDA approval. Moxe also produced complete remissions in children with drug resistant Acute Lymphoblastic Leukemia and is being developed for the treatment of that disease. Another immunotoxin, SS1P, targets the mesothelin antigen. Mesothelin was discovered by Pastan and his colleague Mark Willingham and is a promising target for cancer immunotherapy, because it is expressed on many cancers: mesothelioma, ovarian, lung, pancreatic stomach cancers and cholangiocarcinoma, but not on essential organs. SS1P has shown anti-tumor activity in a phase I trial when combined with chemotherapy. In a recently completed clinical trial, SS1P was combined with the immunosuppressive drugs cyclophosphamide and pentostatin and produced remarkable major and sustained tumor regressions lasting up to 2 years in patients with advanced chemotherapy resistant mesothelioma. Tumor shrinkage of this magnitude and duration has never before been observed in mesothelioma. Pastan’s current efforts are directed at improving the activity and usefulness of immunotoxins he has developed. One of the major obstacles to the