1D09C3, an mAb specific for MHC-II.

GPC Biotech AG is developing 1D09C3, an anti-MHC class II (HLA-DR) fully human IgG4 antibody isolated by MorphoSys AG (from its HuCAL library of human antibodies), for the potential treatment of hematological malignancies. In December 2006, positive safety data from two phase I clinical trials were reported. Final phase I data were expected in mid-2007; however, no additional data have been released at the time of publication.

CD molecules 2006--human cell differentiation molecules.

The Human Leucocyte Differentiation Antigens Workshops (HLDA) have since 1984 provided a forum for the characterization and study of leucocyte surface molecules and antibodies against them. HLDA devised the CD nomenclature, which is sanctioned by IUIS. The HLDA Council reviewed and modified the objectives of HLDA in 2004, and changed the name of the organization to Human Cell Differentiation Molecules (HCDM) to reflect the broader objectives. Workshop studies under the HCDM banner proceeded during 2005 and early 2006, culminating in a meeting in May 2006. At that meeting the Council, acting as Nomenclature Committee, approved a number of new CD designations and changes to some pre-existing CD designations, which are summarized in this report.

Severely impaired wound healing in the collagenase-resistant mouse.

Collagen in the skin undergoes dramatic reorganization during wound repair. Matrix metalloproteinases degrade and remodel the collagen in a tightly controlled process. The collagenase-resistant mouse, Col1a1(tm1Jae), has been developed to produce collagen type I, which is resistant to degradation by human matrix metalloproteinase 1. These mice grow normally but develop thickened skin with age. We investigated the effect of this mutant collagen on wound repair. Incisional wounds were made on Col1a1(tm1Jae) homozygous mutant (Col1a1(r/r)) and wild-type (Col1a1+/+) mice and these wounds were harvested at 1 and 6 h, 1, 2, 3, 7, 10, 14, and 70 d post wounding. Wound healing was severely delayed in Col1a1(r/r) wounds, with wounds remaining significantly wider than wild-type for the first 2 wk after injury. Reepithelialization of the Col1a1(r/r) wounds took 7 d longer than in the wild-type. The Col1a1(r/r) wounds had a prolonged early inflammatory response. Immunostaining for matrix metalloproteinases revealed significant upregulation of matrix metalloproteinase 13 in Col1a1(r/r) wounds, but minimal changes in other matrix metalloproteinases. There was no significant difference in scarring between Col1a1(r/r) and Col1a1+/+ wounds after 70 d.

Monoclonal antibodies to human cell surface antigens.

Many of the leukocyte cell surface molecules are known by "CD" numbers. In this Appendix, a short introduction describes the history and the use of CD nomenclature and provides a few key references to enable access to the wider literature. This is followed by a table that lists all human molecules with approved CD names, tabulating alternative names, key structural features, cellular expression, major known functions, and usefulness of the molecules or antibodies against them in research or clinical applications.

Characterizing regeneration in the vertebrate ear.

We have previously shown that MRL/MpJ mice have a capacity for regeneration instead of scar formation following an ear punch wound. Understanding the differences that occur between scar-free regeneration or repair with scarring will have great impact upon advances in skin tissue engineering. A key question that remains unanswered in the MRL/MpJ mouse model is whether regeneration was restricted to the ear or whether it extended to the skin. A histological analysis was conducted up to 4 months post-wounding, not only with 2-mm punch wounds to the ear but also to the skin on the backs of the same animals. MRL/MpJ mouse ear wounds regenerate faster than control strains, with enhanced blastema formation, a markedly thickened tip epithelium and reduced scarring. Interestingly, in the excisional back wounds, none of these regenerative features was observed and both the C57BL/6 control and MRL/MpJ mice healed with scarring. This review gives an insight into how this regenerative capacity may be due to evolutionary processes as well as ear anatomy. The ear is thin and surrounded on both sides by epithelia, and the dorsal skin is devoid of cartilage and under greater tensile strain. Analysis of apoptosis during ear regeneration is also discussed, assessing the role and expression of various members of the Bcl-2 family of proteins. Ongoing studies are focusing on de novo cartilage development in the regenerating ear, as well as understanding the role of downstream signalling cascades in the process. Identification of such signals could lead to their manipulation and use in a novel tissue-engineered skin substitute with scar-free integration.

Location of injury influences the mechanisms of both regeneration and repair within the MRL/MpJ mouse.

The adult MRL/MpJ mouse regenerates all differentiated structures after through-and-through ear punch wounding in a scar-free process. We investigated whether this regenerative capacity was also shown by skin wounds. Dorsal skin wounds were created, harvested and archived from the same animals (MRL/MpJ and C57BL/6 mice) that received through-and-through ear punch wounds. Re-epithelialization was complete in dorsal wounds in both strains by day 5 and extensive granulation tissue was present by day 14 post-wounding. By day 21, wounds from both strains contained dense amounts of collagen that healed with a scar. The average wound area, as well as alpha-smooth muscle actin expression and macrophage influx were investigated during dorsal skin wound healing and did not significantly differ between strains. Thus, MRL/MpJ mice regenerate ear wounds in a scar-free manner, but heal dorsal skin wounds by simple repair with scar formation. A significant conclusion can be drawn from these data; mechanisms of regeneration and repair can occur within the same animal, potentially utilizing similar molecules and signalling pathways that subtly diverge dependent upon the microenvironment of the injury.

Variable impairment of wound healing in the heterozygous collagenase-resistant mouse.

Collagen undergoes dramatic reorganization during wound repair. Matrix metalloproteinases degrade and remodel collagen in a tightly controlled process. The collagenase-resistant mouse, Col1a1(tm1Jae), produces type I collagen, which is resistant to degradation by human matrix metalloproteinase 1. These mice grow normally but develop thickened skin with age. We have previously reported that the early wound repair response in homozygous mutant (Col1a1(r/r)) mice is delayed compared to wild type (Col1a1(+/+)). However, the late-stage scar of Col1a1(r/r) wounds was not significantly altered compared to Col1a1(+/+). Here we have investigated the response of heterozygous mice (Col1a1(+/r)) to wounding, not previously reported. Wound reepithelialization was delayed to a similar degree to wounds in the Col1a1(r/r) mice. However, the recovery of impaired wound contraction was faster in Col1a1(+/r) than in Col1a1(r/r) mice, but still slower than in wild-type animals. Analysis of wound protein extracts showed expression of some matrix metalloproteinases was prolonged in both the Col1a1(r/r) and Col1a1(+/r) wounds compared to wild type. We suggest the partial resistance of collagen to collagenase-mediated degradation in the heterozygous animals causes equivalent impairment of keratinocyte migration compared to homozygous collagenase-resistant mice, but that wound contraction during late-stage healing is only partially retarded.