Autologous Tumor Infiltrating Lymphocytes MDA-TIL in Treating Patients With Recurrent or Refractory Ovarian Cancer, Colorectal Cancer, or Pancreatic Ductal Adenocarcinoma

Subjects must be willing and able to provide informed consent

Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1 at enrollment and within 7 days of initiating lymphodepleting chemotherapy

Subjects must have an area of tumor amenable to excisional biopsy (core biopsies may be allowed) for the generation of TIL separate from, and in addition to, a target lesion to be used for response assessment

Any prior therapy directed at the malignant tumor, including radiation therapy, chemotherapy, and biologic/targeted agents must be discontinued at least 28 days prior to tumor resection for preparing TIL therapy

Absolute neutrophil count (ANC) \>= 1000/mm\^3 (within 7 days of enrollment)

Hemoglobin \>= 9.0 g/dL (transfusion allowed) (within 7 days of enrollment)

Platelet count \>= 100,000/mm\^3 (within 7 days of enrollment)

Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) and aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) \< 2.5 x the upper limit of normal (ULN)

* Patients with liver metastases may have liver function test \[LFT\] =\< 5.0 x ULN (within 7 days of enrollment)

Calculated creatinine clearance (Cockcroft-Gault) \>= 50.0 mL/min (within 7 days of enrollment)

Total bilirubin =\< 1.5 x ULN (within 7 days of enrollment)

Prothrombin time (PT) \& activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (correction with vitamin K allowed) unless subject is receiving anticoagulant therapy (which should be managed according to institutional norms prior to and after excisional biopsy) (within 7 days of enrollment)

Negative serum pregnancy test (female subjects of childbearing potential) (within 7 days of enrollment)

Subjects must not have a confirmed human immunodeficiency virus (HIV) infection

Subjects must have a 12-lead electrocardiogram (EKG) showing no active ischemia and Fridericia's corrected QT interval (QTcF) less than 480 ms

Subjects must also have a negative dobutamine stress echocardiogram before beginning treatment

Subjects of childbearing potential must be willing to practice an approved highly effective method of birth control starting at the time of informed consent and for 1 year after the completion of the lymphodepletion regimen. Approved methods of birth control are as follows: hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation or hysterectomy; subject/partner status post vasectomy; implantable or injectable contraceptives; and condoms plus spermicide

Able to adhere to the study visit schedule and other protocol requirements

Pulmonary function tests (spirometry) demonstrating forced expiratory value (FEV) 1 greater than 65% predicted or forced vital capacity (FVC) greater than 65% of predicted

Ovarian cancer cohort only: Subjects must have high grade non-mucinous histology (carcinosarcomas are allowed)

Ovarian cancer cohort only: Subjects must have failed at least two prior lines of chemotherapy (i.e. frontline adjuvant chemotherapy plus one additional line for recurrent/progressive disease), or have platinum resistant disease

Colorectal cohort only: Subjects with colorectal adenocarcinoma must have metastatic disease that is considered incurable with currently available therapies and have derived maximal benefit from or have become refractory to frontline conventional therapy (e.g. leucovorin calcium \[calcium folinate\], 5-fluorouracil and oxaliplatin \[FOLFOX\], leucovorin calcium, 5-fluorouracil, and irinotecan \[FOLFIRI\]).

Colorectal cohort only: Subjects should have low disease burden such that in the treating physician's opinion the patient would not require additional intervening treatment for 7-8 weeks (required for TIL harvest and manufacturing)

Pancreatic adenocarcinoma cohort only: Subjects must have histologically or cytologically documented diagnosis of PDAC with oligo-metastatic disease

Pancreatic adenocarcinoma cohort only: Subjects must have progressed on, or received maximal benefit from, front-line therapy

Pancreatic adenocarcinoma cohort only: Patients may have received unlimited lines of prior standard of care therapy

What this study is about