Antibodies against GD2 ganglioside can eradicate syngeneic cancer micrometastases

After 10 years of clinical trials in patients with advanced cancer, monoclonal antibodies (mAbs) against cell surface antigens have not lived up to their initial promise. One such cell surface antigen is the ganglioside GD2. GD2 is richly expressed at the cell surfaces of human neuroblastomas, sarcomas, and melanomas. We have described a murine lymphoma (EL4) that is syngeneic in C57BL/6 mice and expresses GD2, a mAb against GD2 (mAb 3F8), and we have prepared a conjugate vaccine (GD2-keyhole limpet hemocyanin plus immunological adjuvant QS-21) that consistently induces antibodies against GD2. We demonstrate here, for the first time in a syngeneic murine model, that passively administered and vaccine-induced antiganglioside antibodies prevent outgrowth of micrometastases, and we use this model to establish some of the parameters of this protection. The level of protection was proportional to antibody titer. Treatment regimens resulting in the highest titer antibodies induced the most protection, and protection was demonstrated even when immunization was initiated after tumor challenge. Treatment with 3F8 1, 2, or 4 days after i.v. tumor challenge was highly protective, but waiting until 7 or 10 days after challenge resulted in minimal protection. The results were similar whether number of liver metastases or survival was used as the end point. These results suggest that unmodified mAbs or antibody-inducing vaccines against GD2 (and possibly other cancer cell surface antigens) should be used exclusively in the adjuvant setting, where circulating tumor cells and micrometastases are the primary targets.     

Thickness of human cornea measured by topographic pachometry

In the hands of trained user, the topographic pachometer proves to be an instrument of acceptable clinical precision (standard deviation = 0.006mm). An examination of corneal thinning during waking hours revealed a rate of thinning which was greatest upon lid opening and which declined uniformly throughout the day (p = 0.01). An investigation into menstrually related change in corneal thickness revealed that at least 122 subjects would be required to investigate this change on an acceptable statistical basis (p = 0.05).     

2 types of neuromuscular junction in the pharyngeal retractor muscle of snails

The pharyngeal retractor muscle of Helix lucorum is innervated by two symmetrical nerves which contain axons of two types forming myoneural junctions with the muscle cells. Type I junctions correspond to thick axons. These axon terminals which contain a large number of spherical, clear vesicles (41 +/- 5 nm) and a smaller number of dense-cored vesicles (67 +/- 3 nm) make contacts mainly with noncontractile sarcoplasmic processes of muscle cells. Type II junctions correspond to thin axons containing many of granules. Their axon terminals contact with contractile parts of muscle cells and contain a heterogenous population of vesicles: small spherical clear vesicles (44 +/- 2 nm), dense-cored vesicles and numerous irregularly outlined granules with fine-granular content (135 +/- 5 nm). Space between muscle cell is usually wide (50 nm and more) with the exception of sarcoplasmic processes where the gap may be less than 10 nm.