Phylogica (ASX
YC) is the owner of a peptide library containing the extraordinary richness and
diversity of nature. We are using these libraries to develop a drug delivery platform capable of
reaching the highest value drug targets located inside cells. Our delivery platform enables drug
cargoes to cross the cell membrane and directly reach their target.
27 July 2018:
PYC is pleased to announce successful in vivo results in the evaluation of its peptide vaccine
program.
Highlights:
- PYC’s Cell Penetrating Peptides (CPPs) elicit a substantially stronger CD8+ T cell
expansion than the ‘gold standard’ CPP ‘TAT’ in vivo;
- Phylogica’s CPPs triggered an antigen-specific immune response similar in magnitude to
that raised against a Herpes Simplex Virus (HSV) infection (an indication of the strength
of T cell response to be expected from a healthy mouse in response to a strong viral
stimulus);
- In a complementary experiment, the T-cells generated in response to the vaccination
had the ability to kill cells expressing the receptor that they are created to recognise
(target cells); and
- In combination, the experiments demonstrate the efficacy of the CPP-antigen conjugate
in stimulating a CD8+ T cell immune response that is capable of recognising and killing
the target cell.
The results
Phylogica’s peptide vaccine program continues to produce encouraging in vivo data and has
now been expanded beyond oncology to include viral illnesses that can be treated via the
same vaccination strategy (T cell expansion and effector function).
In the most recent in vivo experiments, mice were treated with a range of different CPPs joined
to a common antigen from HSV capable of triggering the creation of cytotoxic CD8+ T-cells
when delivered into the cytoplasm (across the cell membrane) of dendritic cells. After
administration of the various CPP-antigen vaccines and allowing time for the generation of an
immune response, spleens were taken from the mice to measure the levels of CD8+ T-cells that
their immune system had created that were specific to the antigen introduced by the CPP.
Phylogica’s CPPs produced the greatest expansion in CD8+ T cells across all groups of treated
mice. The level of T-cell expansion for Phylogica’s CPPs approached that seen in response to
HSV (a strong viral stimulus).
In a complementary experiment, the vaccinated mice also received cells expressing the HSV
antigen. This experiment simulates a disease state such as a virus or cancer where the target
cells express the receptor towards which the vaccine was directed. The CD8+ T-cells stimulated
by the vaccine were able to recognise and kill the target cells which expressed the HSV antigen
with a high degree of efficiency – confirming that the CPP-antigen vaccination approach is
effective both at stimulating a CD8+ T-cell response and the effector function of those CD8+ T-
cells in recognising and killing their target.
The peptide vaccine program continues to progress in the context of multiple different antigens
(cargoes) and disease indications towards its ultimate read-out of complementarity to existing
therapies in each of these indications to demonstrate improved treatment efficacy.
(20min delay)