Gemcitabine and Ex Vivo Expanded Allogenic Universal Donor, TGFβi Natural Killer (NK) Cells with or Without Naxitamab (Danyelza) for the Treatment of Patients with Metastatic, GD2 Expressing, HER2 Negative Breast Cancer

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed, HER2 negativemetastatic breast cancer that is historically GD2 expressing (e.g., triple negativebreast cancer, metaplastic breast cancer, high grade estrogen positive breastcancer) with available archival tissue. Well differentiated neuroendocrine tumor (NETs) are not eligible for this trial since GD2 expression is unknown. GD2expression is not required for eligibility but a primary tumor paraffin block isrequired at enrollment for assessment of GD2 expression

• Patients must have measurable disease, per Response Evaluation Criteria in SolidTumors (RECIST 1.1) for the evaluation of measurable disease

• Patients must have received at least one prior treatment for metastatic disease andprogressed on treatment or been intolerant to treatment

• Female or male >=18 years

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Absolute neutrophil count >= 1,500/mcL (> 1.5 X 10^6/L)

• Platelets >= 100,000/mcL

• Hemoglobin >= 9 mg/dL (transfusion to obtain hemoglobin >= 9 mg/dL within 24 hoursprior to dosing is allowed)

• Serum creatinine =< 1.5 X upper limit of normal (ULN) or measured or calculatedcreatinine clearance (CrCl) >= 60 mL/min for participant with creatinine levels > 1.5 X institutional upper limit of normal (ULN) (Glomerular filtration rate [GFR]can also be used in place of creatinine or CrCl)

• Patients must have adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =< 3 X ULN and total bilirubin < 1.5X ULN, unless known diagnosis of Gilbert's syndrome, where bilirubin =< 5 mg/dL willbe permitted. Gilbert's syndrome will be defined as elevated unconjugated bilirubin,with conjugated (direct) bilirubin within the normal range and less than 20% of thetotal. Total bilirubin will be permitted up to 5 mg/dL, if patients have historicalreadings consistent with the definition of Gilbert's syndrome prior to enteringstudy. Adequate hepatic function for patients with known liver metastases is definedas AST and ALT levels ≤ 5 X ULN

• The effects of the trial agents on the developing human fetus are unknown. However,gemcitabine is known to have negative fetal effects. For this reason: Women ofchildbearing potential must agree to use adequate contraception at study entry, forthe duration of study participation and for 7 months after the last dose of studymedication based upon estimated half-life or receptor occupancy. Adequatecontraception is defined as 2 highly effective methods of contraception (including aphysical barrier). Should a woman become pregnant or suspect she is pregnant whileshe or her partner is participating in this study, she should inform her treatingphysician immediately. Men should refrain from fathering a child using adequatecontraception or donating sperm during the study and for 6 months after the lastdose of study medications. Adequate contraception is defined as 2 highly effectivemethods of contraception (including a physical barrier)

• Patients with well-controlled human immunodeficiency virus (HIV) infection areeligible for trial as long as:

• On an effective anti-retroviral therapy (ART) ˃ 4 weeks and with evidence ofviral-suppression as defined as HIV viral load ˂ 400 copies/mL within the last 3 months

• CD4 > 200 cells/µL within the last 3 months; and

• No reported opportunistic infections within 6 months prior to enrollment,except for the following which will be allowed:

• Esophageal candidiasis treated within last 6 months or currently improvingwith antifungal treatment.

• Oral and/or genital herpes simplex virus (HSV) treated within last 6months or currently improving with antiviral treatment.

• Mycobacterium avium infection in last 6 months or that has been treatedfor at least 1 month

• Patients with evidence of chronic hepatitis B virus (HBV) infection are eligible fortrial as long as the HBV viral load is undetectable on suppressive therapy, ifindicated.

• Patients with history of hepatitis C virus (HCV) infection must have beentreated and cured. For patients with HCV infection who are currently ontreatment, they are eligible if they have an undetectable or unquantifiable HCVribonucleic acid (RNA) 12 weeks or longer after definitive treatmentcompletion.

• Patients must be able to understand and willing to sign a written informedconsent document

• Any adverse events subjects have experienced from prior therapy must have resolvedto =< grade 1 according to National Cancer Institute Common Terminology Criteria forAdverse Events (NCI CTCAE) version 5

Exclusion Criteria:

• Patients who within 3 weeks prior to study enrollment who have receivedchemotherapy, investigational agents, or radiation

• Patients with active brain metastases or leptomeningeal metastases are excluded fromthis clinical trial because they often develop progressive neurologic dysfunctionthat would confound the evaluation of neurologic and other adverse events. However,patients with treated brain metastases are eligible if there is no magneticresonance imaging (MRI) evidence of progression for 6 months after treatment iscomplete and within 28 days prior to the first dose of trial drug. Patientsrequiring immunosuppressive doses of systemic corticosteroids (> 10mg/day prednisoneequivalent) for palliation are excluded

• Patients with a history of another invasive malignancy < 3 years prior to enrollment (patients with non-melanoma skin cancers, carcinoma in situ of the breast or cervixare eligible)

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to agents used in study

• Uncontrolled intercurrent illness including, but not limited to, ongoing activeinfection that requires systemic treatment with ongoing antibiotics (eligible if canstop antibiotics on day of enrollment), unexplained fever (temperature > 38.1˚celcius [C]) within 7 days of initial treatment, unstable angina pectoris,cardiac arrhythmia, or psychiatric illness/social situation that in the opinion ofthe primary investigator would prohibit the patient from complying with studyrequirements

• Patients with bone metastases who have initiated denosumab or a bisphosphonatetherapy within 28 days prior to or after cycle 1 day 1 due to the potential forflu-like symptoms and mild cytokine release syndrome with the initial dose. However,continuation of prior therapy is allowed

• Patients should have no evidence of being immunocompromised as listed below:

• Active, known or suspected autoimmune disease. Patients are permitted to enrollif they have vitiligo, type I diabetes mellitus, residual hypothyroidism due toan autoimmune condition only requiring hormone replacement, psoriasis notrequiring systemic treatment or conditions not expected to recur in the absenceof an external trigger in the opinion of the primary investigator

• Altered immune function that in the judgement of the PI that may affect apatient's ability to adequately engage the immune system and respond to theimmunotherapy agents being administered, including but not limited to:inflammatory bowel disease; active infectious enteritis; eosinophilicenteritis; lupus erythematous; ankylosing spondylitis; scleroderma; multiplesclerosis. These criteria do not include all disease with an immune-relatedcomponent but are not autoimmune in nature or have a primary alteration in thegeneral immune function that may interfere with the vaccine mechanism ofaction, for example celiac disease

• Immunosuppressive therapy post-organ transplant

• Concurrent use of chronic use of systemic steroids, except for physiologicdoses of systemic steroids for replacement, defined as 10mg of prednisone perday or equivalent, or local (topical, nasal, ophthalmic or inhaled) steroid useor prior concomitant use with chemotherapy. Systemic steroids must have beendiscontinued >2 weeks prior to trial start. Prior use of corticosteroids inshort-term schemes (duration shorter than 3 days) for indications such asprophylaxis of reactions to intravenous contrast for imaging studies orchemotherapy-related adverse events (AEs) are not considered part of thisexclusion. Prior use of corticosteroids for brain metastasis ending at least 14days prior to enrollment is not considered part of this exclusion criteria

• Pregnant and breastfeeding women are excluded from this study because of thepotential for teratogenic or abortifacient effects with all of the agents involvedin this trial. Females of childbearing potential who are pregnant, breast feeding,intend to become pregnant, or are not using adequate contraceptive methods or maleswho are not using adequate contraceptive methods. Women of childbearing potentialmust agree to use two methods of adequate contraception at study entry be used forthe duration of study participation and for at least 7 months for women and 6 monthsfor men after the final dose of any study-related medications

• Clinically significant cardiomyopathy, coronary disease, myocardial infarction,chronic heart failure (CHF) (New York Heart Association class III or IV orhospitalization for CHF), ejection fraction < 50% or cerebrovascular accident within 6 months prior to enrollment

• Patients with a history of myocarditis are excluded due to the potential ofmyocarditis with anti-PD-L1 antibodies or other immunotherapies

• Patients who have received any live vaccines within 30 days prior to enrollment (inactivated vaccines including COVID vaccines are allowed)

• Any other condition, which would, in the opinion of the principal investigator thesubject is a poor candidate for the clinical trial or would jeopardize the subjector the integrity of the data obtained