BAT is an immune-modulatory
monoclonal antibody that exhibits strong lymphocyte-mediated anti-
tumor activity against a variety of murine and human
tumors.
Peptide A is a
vaccine we have developed by screening a
phage display peptide library on
BAT monoclonal antibody. Anti-
tumor activity was obtained in mice inoculated with
B16 melanoma by either a single injection with BAT or immunization with
peptide A. The aim of this study was to follow and compare histopathologically the process of prevention of
melanoma metastases in lungs of treated and immunized mice. Mice were sacrificed on different days after
tumor inoculation, their lungs were weighed and the number of
metastases was counted. The lungs were then fixed in
formalin, embedded in
paraffin, and stained with
hematoxylin and
eosin. Histological examination of
tumor inoculated mice on day 10 revealed the existence of microscopic
melanoma lesions (0.01-0.012 mm) that increased gradually in number and size and on day 21, most of the
metastases were large and spanned entire lobes, from the pleura to the hilum, measuring up to 3.5 mm and coexisting with scattered, small
metastases showing the same morphology and pattern of lung involvement. On day 24, the lungs of untreated mice were massively infiltrated by coalescing
metastases replacing up to 50% of the lung tissue and measuring up to 7.0 mm. The number of lung
metastases and weight was dramatically decreased by a single injection of
BAT monoclonal antibody ten days post
tumor inoculation. The treated mice clearly had fewer and smaller
metastases in different mice at the different days post
tumor inoculation. On day 21, there were few small
metastases measuring up to 1.6 mm and on day 24 no lung
metastases were detected in this group that appeared with a completely normal lung structure. Immunization with
peptide A started one day post
tumor inoculation and was compared to immunization with control
peptide N. Fourteen days post
tumor inoculation, mice immunized with
peptide A had only 1-2
metastases (0.012-0.076 mm) and on day 24 ranged up to 2 mm compared to control immunized mice where the
tumor developed up to 5-7 mm. Foci of
lung inflammation in both the untreated, treated or immunized mice were rare, small, and not preferentially associated with the lung
metastases. They were composed mainly of small lymphocytes and a few macrophages. This study is the basis of histopathological understanding of
metastases prevention in lungs of mice immunized or treated by
BAT monoclonal antibody.