CD22 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B cell receptor and its co-receptor CD19. Recently it was reported that most human lung cancer cells and cell lines express CD22 making it an important new lung cancer therapeutic target (Can Res 72:5556, 2012). The objective of our studies was to independently validate these results with the goal of testing the efficacy of our CD22 immunotoxins on lung cancer cell lines. As determined by qRT-PCR analysis, we found that levels of CD22 mRNA in a panel of human lung cancer cell lines were 200–60,000- fold lower than those observed in the human CD22+ Burkitt’s lymphoma cells, Daudi. Using flow cytometry with a panel of CD22 monoclonal antibodies and Western blot analyses, we could not detect surface or intracellular expression of CD22 protein in a panel of lung cancer cell lines. In addition, the in vitro proliferation of the lung tumor cell lines was not affected by CD22 antibodies or our highly potent anti-CD22 immunotoxin. By contrast, CD22+ Daudi cells expressed high levels of CD22 mRNA and protein and were sensitive to our CD22 immunotoxin. Importantly, primary non-small cell lung cancers from over 250 patient specimens did not express detectable levels of CD22 protein as assessed by immunohistochemistry. We conclude that CD22 is not expressed at measurable levels on the surface of lung cancer cells and that these cells can not be killed by anti-CD22 immunotoxins.

A 45-year-old man was hospitalized with abdominal pain. He was diagnosed with superior mesenteric vein thrombosis with mesenteric ischemia and treated with partial small bowel resection and 2 weeks of enoxaparin while hospitalized. Three weeks later, he presented again with abdominal pain. A computed tomography (CT) scan demonstrated fluid collections adjacent to the ascending colon and bowel wall thickening with intestinal pneumatosis consistent with ischemic bowel. Superior mesenteric vein thrombosis was redemonstrated on CT scan. An intravenous course of piperacillin-tazobactam was started, and an exploratory laparotomy with bowel resection was performed. Postoperatively, intravenous heparin was started. One day following surgery, a CT scan demonstrated a new left femoral vein thrombosis and pulmonary embolism. Laboratory data are shown in Table 1. Answer B. Replace heparin with argatroban for heparin-induced thrombocytopenia.

746 Background: Peritoneal carcinomatosis (PC) is the intraperitoneal spread of cancer. Optimal treatment for PC is controversial. Systemic chemotherapy offers limited benefit (Franko, 2011). Intraperitoneal (IP) chemotherapy following cytoreductive surgery (CRS) improves outcomes (Verwaal, 2008). Oxaliplatin (Ox), capecitabine, and bevacizumab are standard agents for the treatment of metastatic colorectal cancer (CRC). Evidence suggests benefit of IP Ox at high doses. However, the optimal dose of IP Ox combined with standard systemic therapy is unclear. Methods: We conducted an IRB-approved phase I dose-escalation study of IP Ox D1 at 25mg/m2-100mg/m2, with systemic bevacizumab D1 at 5mg/kg, and capecitabine 850mg/m2 BID for 7 days (cycle = 14 days), in patients with PC from appendiceal or CRC after CRS. The primary aim was to determine the recommended phase II dose (RP2D)/maximum tolerated dose (MTD) for this regimen. Dose limiting toxicities (DLTs) were assessed during cycle 1. DLTs included grade 3 or 4 non-hematological toxicities, or grade 4 hematological toxicities. Results: 18 patients (12 females, median age 56) were enrolled on the study. No DLTs were observed during cycle 1 in the first 4 cohorts. One DLT (abdominal pain) was observed in cohort 5. Another patient in cohort 5 experienced grade 3 abdominal pain soon after cycle 2, thus limiting repeated treatment for this cohort. Other toxicities included fatigue (72%), nausea (61%), peripheral neuropathy (50%), constipation (50%), mucositis (39%) and dizziness (39%). See table below for average # of cycles per cohort and responses. Conclusions: IP Ox combined with capecitabine and bevacizumab is feasible. Our recommended dose for IP Ox is 85 mg/m2 with systemic therapy (cohort 4). An expansion cohort is underway for this dose level. Based on these data, further investigation of IP Ox with systemic chemotherapy for PC is warranted. Clinical trial information: NCT01061515. [Table: see text]