Dual Administration Of Intraperitoneal And Intravenous TROP2-Directed CAR-NK With TGF-Beta Receptor 2 (TGFBR2) Knock Out (KO) Therapy For Colorectal Cancer-Related Peritoneal Carcinomatosis: A Phase 1/2 Trial ("Chip-CRC Trial")

Eligibility Criteria * Subjects must be 18 years or older. Because no dosing or adverse event data are currently available on the use of IP/IV TROP2 CAR/IL-15 TGFBR2 KO NK Cell Therapy + Cetuximab in participants 3 liver metastases, \>5 lung metastases, or \>8 metastases combined between all extraperitoneal sites will not be included even in the setting of measurable peritoneal disease. If a participant has peritoneal-predominant disease with ≤ 8 total extraperitoneal metastases, they may be included at the discretion of the PI. * Subjects must be at least 4 weeks from their last dose of systemic cytotoxic chemotherapy at the time of their diagnostic laparoscopy (DL)/IP catheter placement or 6 weeks if the chemotherapy regimen included Bevacizumab. Participants must be at least 4 weeks from their last dose of systemic cytotoxic chemotherapy at the time of their lymphodepleting (LD) chemotherapy. * Subjects must be willing to undergo DL and IP catheter placement along with scheduled peritoneal fluid/peripheral blood draws and biopsies. * Subjects must have adequate organ function as defined in the following table. Specimens must be collected within 10 days prior to the start of study treatment. * Participant s must have histologically confirmed microsatellite stable (MSS) CRC-related PM that is not amenable to curative resection (participant determined not to be a candidate for CRS +/- HIPEC by surgical oncologist with expertise in peritoneal surface malignancies) and for which standard curative treatment is no longer effective (they have progressed through at least one line of standard systemic chemotherapy and/or are intolerant of systemic chemotherapy in the opinion of their primary medical oncologist). • MSS status must be confirmed either by immunohistochemistry (IHC) or polymerase chain reaction (PCR)-based genetic analysis. Participants with MSI-H tumors are ineligible. • Participant must have never undergone a prior HIPEC operation (CRS without HIPEC is OK) • Participant s with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participant s should be class 2B or better. * Women of childbearing potential (WOCBP): The effects of CAR NK therapy on the developing human fetus are unknown. For this reason and because lymphodepleting (LD) chemotherapy agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 months after completion of CAR NK therapy administration. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female participant s, between the onset of menses (as early as 8 years of age) and 55 years unless the participant presents with an applicable exclusionary factor which may be one of the following: * Postmenopausal (no menses in greater than or equal to 12 consecutive months). o History of hysterectomy or bilateral salpingo-oophorectomy. * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy). * History of bilateral tubal ligation or another surgical sterilization procedure. 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 post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. See Appendix 1 for more details. * Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of TROP2 CAR/IL-15 TGFBR2 KO NK cells therapy administration. Exclusion Criteria * Pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with screening visit through 4 months after last dose of trail treatment (TROP2 CAR/IL-15 TGFBR2 KO NK cell therapy). If a WOCBP has a positive urine pregnancy test within 72 hours prior to administration of LD chemotherapy that cannot be confirmed as negative, a serum pregnancy test will be required. * Participants with BRAFV600E mutated tumors (determined by Next Generation Sequencing, NGS) will be excluded. * Has received systemic anti-cancer therapy within 4 weeks of their scheduled diagnostic laparoscopy (DL)/IP catheter placement or 6 weeks if the regimen included Bevacizumab. Or has received systemic chemotherapy of any kind within 4 weeks prior to the time of their lymphodepleting (LD) chemotherapy. * Participants must have recovered from all AEs due to previous therapies to Grade ≤1 or baseline. Participants with Grade ≤2 neuropathy, alopecia, or other AEs may be deemed eligible at the discretion of the PI. If a participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. * Has received prior radiotherapy within 2 weeks of the start of study intervention (DL). Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout if permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease. * Has received a live vaccine within 30 days prior to the initiation of LD chemotherapy. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus-Calmette-Guérin (BCG), and typhoid vaccines. Seasonal influenza and COVID vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed. * Is currently receiving another investigational agent or has used an investigational device within 6 weeks prior to the first dose of study intervention. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 6 weeks after the last dose of the previous investigation agent. * Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose LD. * High-volume extra-peritoneal visceral metastases to include but are not limited to, high volume (\>3) liver metastases, high volume (\>5) lung metastases, CNS metastases (any number) and/or carcinomatous meningitis, bone metastases (any number) will be excluded. Any participant s with \>8 total metastases combined between all visceral extraperitoneal sites will also be excluded. Low volume liver (≤3) and/or lung (≤5) metastases that have been treated, are amendable to locoregional therapy, and are not an immediate threat to life may be included at the discretion of the PI if the total number of visceral extraperitoneal metastases remains ≤ 8. Individuals with nodal metastases and/or abdominal wall metastases similarly may be included at the discretion of the PI. * Active autoimmune disease that has required systemic treatment in the past 2 months (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed. * History of interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. * Serious active infection requiring intravenous systemic therapy. * Uncontrolled Human Immunodeficiency Virus (HIV) infection. Participants with HIV who have an undetectable viral load and a CD4 count of at least 400 cells/mm3 may participate. * Known Hepatitis B Virus (HBV) not on suppressive therapy or with detectable viral load on suppressive therapy. If undetectable viral load on suppressive therapy, OK to participate. * Known Hepatitis C Virus who has not been treated or cured, or who is currently being treatment with a detectable viral load. If cured or being treated with an undetectable viral load, OK to participate. * Known history of active Tuberculosis (TB). * History or current evidence of any condition, therapy, or laboratory abnormalities that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Has had allogeneic tissue/solid organ transplant. * Clinically significant cardiovascular disease within 12 months from the first dose of study intervention, including New York Heart Association (NYHA) Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular event, or cardiac arrhythmia associated with hemodynamic instability. Note: medically controlled arrhythmia would be permitted. * Prolonged QTcF interval to \>480 ms. * Bleeding or thrombotic disorders or subjects at risk of severe hemorrhage. Subject with known deep vein thrombosis/pulmonary embolism that are under appropriate anticoagulation treatment are eligible. * Radiographic distribution of disease that in the investigator's opinion would impart excessive risk to participation to this protocol. * Active peritonitis or diverticulitis. * Medical or surgical history that in the treating physician's opinion would make the subject not a suitable candidate for intraperitoneal therapy. Examples would include surgically documented extensive intraperitoneal adhesions, prior HIPEC operation, or large volume ascites. * History of severe hypersensitivity reaction with biologic therapies (e.g. monoclonal antibodies).