Personalized Adoptive Cellular Therapy Targeting MDS Stem Cell Neoantigens (PACTN)

PACTN is manufactured by a novel method to employ cancer-specific somatic variants
(mutations) as a means to immunize autologous T lymphocytes to specifically kill cancer cells
bearing the protein products of the mutations.

The PACTN method is based on the premise that somatic DNA mutations that cause cancer often
give rise to proteins with an altered amino acid sequence. Peptides derived from these
proteins, if expressed in the context of MHC Class I or II may be perceived as "non-self" by
the immune system; that is, they may be perceived as neoantigens (aka, neoepitopes). Such
neoantigens could therefore serve as immunogenic targets for the development of
patient-specific, personalized T cell mediated immunotherapy.

Inclusion Criteria:

- Confirmed diagnosis of MDS according to the French-American-British (FAB) criteria.
Subjects with MDS must have intermediate, high, or very high risk IPSS-R scores and
cytopenia of at least one lineage.

- Relapsed/refractory disease, or inadequate response to at least 6 cycles of
hypomethylating (HMA) therapy or subjects who decline HMA therapy. Subjects must not
have received any MDS or AML directed therapy for >28 days prior to receiving the
study treatment.

- Subjects who have opted not to undergo allogeneic hematopoietic stem cell
transplantation or for whom no donor is available and who are not deemed eligible for
high intensity chemotherapy.

- Age >18 year at the time of obtaining informed consent, male or female.

- An Eastern Cooperative Oncology Grou (ECOG) performance status score of 0, 1, or 2.

- Adequate organ function.

- Seronegative test for HIV-1/2 and hepatitis C antibodies (HCV), and a negative test
for Hepatitis B antigen (HBsAg). If hepatitis C antibody test is positive, then the
subject must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.

- Women of childbearing potential must have negative pregnancy test prior to initiating
study treatment.

- Life expectancy >6 months at time of screening.

- Ability to adhere to the protocol requirements and study visit schedule.

Exclusion Criteria:

- Subjects who anticipate use of other investigational or non-investigational agents for
the treatment of MDS during the study period, aside from a stable dose of
erythropoietin stimulating agent started >8 weeks prior to screening for this study.

- Subjects who have received investigational agents, cytotoxic chemotherapy, or
radiotherapy within 28 days prior to entering the study, or who have not recovered
from AEs dur to agents administered more than 28 days earlier.

- Subjects who are less than 21 days from surgery or have insufficient recovery from
surgical-related trauma or wound healing.

- Prior history of allogeneic hematopoietic stem cell transplantation.

- Current use of granulocyte colony-stimulating factory (G-CSF) or GM-CSF.

- History of major organ autoimmune disease.

- Concurrent immunosuppressive therapy. A stable dose of prednisone <10 mg daily or
inhaled corticosteroids are allowed.

- Any form of primary immunodeficiency.

- Active bacillus tuberculosis (TB) or any other active or uncontrolled infection.

- Pior history of treated malignancy in the past 2 years. Subjects with non-melanoma
skin cancer, localized prostate cancer, and carcinoma in situ of the breast of cervix
are allowed.

- Impaired cardiac function.

- Pregnant women are excluded from this study as the proposed treatment has not been
well studied in pregnant subjects.

- Any other medical or psychiatric disorders, or social situation, that would, in the
investigator's opinion, place the subject at unacceptable risk if he/she participates
in the study.