Safety Study Of Chemotherapy Combined With Dendritic Cell Vaccine to Treat Breast Cancer

Recent studies have shown that human breast cancers can be immunogenic, and that enhancing
the immune effector function already present may augment the cytotoxic effects of standard
therapies.

vaccination remains the most attractive strategy because of its expected inducement of both
therapeutic T cell immunity (effector T cells) and protective T cell immunity (tumor-specific
memory T cells that can control tumor relapse). Several clinical studies have now
demonstrated that immunity against tumor antigens can be enhanced in cancer patients by
vaccination with ex vivo-generated tumor antigen-loaded dendritic cells (DCs). This strategy
capitalizes on the unique capacity of DCs to prime lymphocytes and to regulate and maintain
immune responses.

Our goals are to boost T cell immunity targeted against breast cancer utilizing a tumor
antigen-loaded DC vaccine, to enhance chemotherapy effectiveness and decrease tumor
metastagenicity, and to decrease the recurrence rates of LA TNBC and ER+/HER2- BC. Patients
will be treated with a combination of antigen-loaded DC vaccinations along with standard
preoperative chemotherapy, to improve immunogenicity and to increase the pCR rate achieved
with standard therapy. The trial will consist of 2 patient cohorts: TNBC and ER+/HER2- BC.

- Inclusion Criteria:

A patient will be considered for enrollment in this study if all of the following criteria
are met:

1. Female patients ≥18 years of age.

2. Have either:

1. locally advanced TNBC defined as invasive ductal cancer; ER- tumors with <10% of
tumor nuclei immunoreactive; PR- tumors with <10% of tumor nuclei immunoreactive;
T3 or T4 disease, regardless of nodal status (T2 disease is eligible if there are
positive lymph nodes present by physical exam or imaging evaluation or
histological evaluation, OR

2. High-risk ER+ breast cancer defined as grade 3 invasive ductal or mixed
ductal/lobular cancers, or grade 2 with Ki67 ≥20%; node positive as evidenced by
physical exam or imaging evaluation or histological evaluation. 3. HER2- negative
breast cancer. If HER2-, it is defined as follows:

1. FISH-negative (FISH ratio <2.0), or

2. IHC 0-1+, or

3. IHC 2+ AND FISH-negative (FISH ratio<2.0)

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 5. Adequate
hematologic function, defined by:

1. Absolute neutrophil count (ANC) >1500/mm3

2. Platelet count ≥100,000/mm3

3. Hemoglobin >9 g/dL (in the absence of red blood cell transfusion) 6. Adequate liver
function, defined by:

a. AST and ALT ≤2.5 x the upper limit of normal (ULN) b. Total bilirubin ≤1.5 x ULN 7.
Adequate renal function, defined by:

a. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥60 ml/min 8. Patients
with previous history of invasive cancers (including breast cancer) are eligible if
definitive treatment was completed more than 5 years prior to initiating current study
treatment, and there is no evidence of recurrent disease. 9. Eligible for treatment with
paclitaxel, doxorubicin, cyclophosphamide and carboplatine. 10.Patient must be accessible
for treatment and follow-up. 11.Patients must be willing to undergo research biopsies to
obtain breast cancer tissue for whole exome sequencing and evaluation of tumor immune
microenvironment. 12.All patients must be able to understand the investigational nature of
the study and give written informed consent prior to study entry.

- Exclusion Criteria:

A patient will be ineligible for inclusion in this study any of the following criteria are
met:

1. Evidence of metastatic disease on bone scan and CT scan of chest/abdomen (or PET CT
scan). Patients with intrathoracic metastatic adenopathy are eligible.

2. Active infection or unexplained fever >38.5°C during screening.

3. Active infections including viral hepatitis and HIV.

4. Active asthma or other condition requiring steroid therapy.

5. Autoimmune disease including lupus erythematosus or rheumatoid arthritis. Topical or
inhaled corticosteroids are allowed.

6. Patients who are currently receiving or who have received previous systemic therapy
for breast cancer (eg, chemotherapy, antibody therapy, targeted agents).The use of an
LHRH agonist during chemotherapy in premenopausal women who wish to preserve ovarian
function is allowed, but is not required.

7. Women who are pregnant or lactating. All patients with reproductive potential must
agree to use effective contraception from time of study entry until at least 3 months
after the last administration of study drug.

8. Have a NYHA Class III or IV CHF or LVEF <55%. Patients with significant cardiac
disease history within 1 year or ventricular arrhythmias requiring medication are also
excluded.

9. Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation such as:

1. severe impaired lung functions as defined as spirometry and DLCO that is 50% of
the normal predicted value and/or O2 saturation that is 88% or less at rest on
room air

2. uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN

3. liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class
C).

10. History of any other disease, physical examination finding, or clinical laboratory
finding giving reasonable suspicion of a disease or condition that contraindicates use
of an investigational drug, or that might affect interpretation of the results of this
study, or render the patient at high risk for treatment complications.

11. Any other investigational or anti-cancer treatments while participating in this study.

12. Any other cancer