Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues.

Gastrointestinal cancers (GICs) and neuroendocrine tumors (NETs) are often refractory to therapy after metastasis. Adoptive cell therapy using chimeric antigen receptor (CAR) T cells, though remarkably efficacious for treating leukemia, is yet to be developed for solid tumors such as GICs and NETs. Here we isolated a llama-derived nanobody, VHH1, and found that it bound cell surface adhesion protein CDH17 upregulated in GICs and NETs. VHH1-CAR T cells (CDH17CARTs) killed both human and mouse tumor cells in a CDH17-dependent manner. CDH17CARTs eradicated CDH17-expressing NETs and gastric, pancreatic and colorectal cancers in either tumor xenograft or autochthonous mouse models. Notably, CDH17CARTs do not attack normal intestinal epithelial cells, which also express CDH17, to cause toxicity, likely because CDH17 is localized only at the tight junction between normal intestinal epithelial cells. Thus, CDH17 represents a class of previously unappreciated tumor-associated antigens that is 'masked' in healthy tissues from attack by CAR T cells for developing safer cancer immunotherapy.

Choosing medical or surgical terminations of pregnancy in the first trimester: what is the difference?

BACKGROUND: Women seeking termination of pregnancy in Auckland, New Zealand can chose between medical and surgical options up to eight weeks gestation. AIMS: To assess demographic differences or changes over time between proportions of women choosing medical or surgical abortions at a single centre and determine whether changing the mifepristone-misoprostol interval from two to one day impacted on outcomes. METHODS: Retrospective audit of two consecutive years (December 2005-November 2006 and December 2006-November 2007) of first-trimester surgical and medical terminations where the mifepristone-misoprostol interval was reduced from two to one day between years. Analysis using descriptive statistics and assessment of probability of observed differences between groups. RESULTS: A total of 1495 terminations were performed in 2005-2006 and 1588 in 2006-2007. No significant difference (P = 0.4) of eligible women choosing medical (21% and 23%) or surgical abortion between years. Ethnicity, age and residency status did not influence choice. Medical termination of pregnancy was more likely in women who were without previous children (P = 0.009), pregnancies (P = 0.02) or terminations (P = 0.04). Medical termination was similarly effective within six hours with either two- or one-day intervals. CONCLUSIONS: Both medical and surgical first-trimester abortions are safe and effective. It is optimal to be able to offer women choice. Reducing the medical interval to one day does not increase adverse outcomes.

First trimester medical termination of pregnancy: an alternative for New Zealand women.

BACKGROUND: First trimester medical terminations of pregnancy (TOP) have been carried out in a private abortion clinic in Auckland from 1 July 2003 to 30 June 2005. AIMS: To audit first trimester medical TOP outcomes over the first 2 years and to compare the demographics and complication rates of women opting for medical TOP with those choosing surgical TOP during this period. METHODS: Retrospective, consecutive case audit of women presenting for a first trimester TOP. Anonymous audit included ethnicity, gestation at first appointment, pain relief requirements, blood loss, timing from the taking of misoprostol to expulsion of products of conception, complications and comparison of outcomes and characteristics between medical termination of pregnancy (MTOP) and surgical termination of pregnancy (STOP). RESULTS: A total of 3311 TOPs were performed over the 2-year study period, including 390 MTOPs (12%). No significant differences were found in age, ethnicity or history of previous TOP between women choosing MTOP or STOP. Gravida 1 and nulliparous women were significantly more likely to choose MTOP. Five per cent (21/390) of women taking mifepristone progressed to STOP. Complications involving hospitalisation occurred in six MTOPs (1.5%) and 18 STOPs (0.6%). CONCLUSIONS: First trimester MTOP is safe and effective and is a realistic alternative for women wanting choice of method in New Zealand.