Novel RNA-lipid Particle (RNA-LP) Vaccine for Anti-PD-1 Antibody Therapy Sensitization

Inclusion Criteria: * Adults ≥ 18 years old * ECOG performance ≤ 2 * Lab values within the specified ranges: * Hemoglobin ≥ 8G/DL * Platelets ≥ 100 thou/cumm * Absolute Neutrophil Count (ANC) ≥ 1000 thou/cumm * Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) * AST and ALT ≤ 2.5 x ULN; If confirmed liver metastases: AST and ALT ≤ 5 x ULN * Creatinine clearance (CrCl) ≥ 15 ml/min (based on modified Cockcroft and Gault formula) * Must have measurable disease that is amenable to surgical sampling for RNA extraction, amplification, and loading of lipid particles * Subjects must not have more than one active malignancy at the time of enrollment (subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen \[as determined by the treating physician and approved by the PI\] may be included) * Written informed consent obtained from the subject. * Participants of childbearing potential must have a negative serum pregnancy test at screening * Participants of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least four months after the last dose of study treatment to minimize the risk of pregnancy. Prior to study enrollment, participants of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. * Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for four months following the last dose of study treatment and must agree to not donate sperm during the study treatment period or for four months following the last dose of study treatment. Additional eligibility criteria for subjects with melanoma: * Patients with stage II, stage III, or resected stage IV melanoma who received anti-PD-1-based therapy in the adjuvant or neoadjuvant setting (either monotherapy or combination therapy) and experienced progressive disease (PD) per RECIST 1.1 during treatment or within 6 months of completing the planned course of therapy. This includes patients who: * Were planned to receive approximately 1 year of anti-PD-1-based therapy in the adjuvant setting but discontinued early due to toxicity and relapsed within 6 months of discontinuation; * Received neoadjuvant anti-PD-1-based therapy (with or without subsequent surgery), including patients planned to complete approximately 1 year of total perioperative anti-PD-1-based therapy (neoadjuvant ± adjuvant), and experienced PD during therapy or within 6 months of completion or discontinuation; * Received short-course neoadjuvant anti-PD-1-based therapy (including combination regimens), underwent surgery, were subsequently managed with surveillance (including those achieving pathologic complete response), and experienced relapse within 6 months of completion of neoadjuvant therapy. * Patients with unresectable or widespread metastatic (stage IV) melanoma who experienced PD per treating physician while receiving anti-PD-1-based therapy (either monotherapy or combination therapy) in any line of treatment. * Patients with unresectable or widespread metastatic (stage IV) melanoma who: * Completed a planned course of anti-PD-1-based therapy (monotherapy or combination), including planned treatment durations of approximately 1 year or 2 years, and experienced PD within 6 months of completion; or * Were planned to receive anti-PD-1-based therapy (for either 1 year or 2 years) but discontinued early due to toxicity and experienced PD within 6 months of discontinuation. * Both cutaneous and non-cutaneous melanoma subtypes (including uveal, mucosal, and acral lentiginous) are eligible. * Patients must: * Have no contraindication to continued immune checkpoint therapy; * Not have rapidly progressive disease requiring urgent alternative therapy; and * Have no other viable approved salvage treatment options available, or decline currently approved salvage therapies. Additional eligibility criteria for subjects with soft tissue sarcoma: * Evidence of spindle cell, pleomorphic, round cell, or epithelioid morphology on pathology suggestive of sarcoma as determined by a sarcoma pathologist * Evidence of progression or resistance to therapy as defined by the treating physician. * Must have measurable disease per RECIST 1.1 * Original tumor site from soft tissue location i.e. lipomatous tissue, musculature, skin * Evidence of unresectable stage II disease; stage III or stage IV disease * Subjects with prior exposure to an immune checkpoint inhibitor (ICI) are eligible for enrollment; however, prior ICI therapy is not required unless receipt of an ICI constitutes part of the FDA-approved standard of care for their disease. Exclusion Criteria: * Subjects that have an active second malignancy, however, previously treated early stage malignancies with no evidence of disease recurrence after 3 years of follow-up will be allowed * Subjects with a history of immune-mediated treatment-related adverse reactions leading to discontinuation of prior aPD1 therapy or severe hypersensitivity reaction to any monoclonal antibody or any other baseline risk in the opinion of the investigator that precludes continued use of aPD1 therapy * Patients with known active and symptomatic brain metastases or leptomeningeal metastases at time of inclusion. Patients with isolated brain lesions that have been treated with stereotactic radiosurgery or surgical resection as part of oligometastatic initial management prior to start of immunotherapy may be eligible as long as they have no new disease and are asymptomatic at time of inclusion. * If patients develop new brain metastases during the time between tumor sampling and vaccine generation and administration, patients may remain on study as long as they can receive definitive stereotactic radiosurgery or surgery to brain metastases and be able to resume systemic therapy within 6 weeks of discovery of new brain metastases. * Subjects who received an investigational drug in another clinical trial must wait 28 days or at least 5 half-lives of the study drug, whichever is shorter, prior to enrollment in this study * Patients must not have required systemic corticosteroids (anything greater than 10mg of prednisone of equivalent, daily) or other immunosuppressive medications within 14 days of the start of trial treatment. * Subjects with known active infection or immunosuppressive disease within seven days prior to tissue collection for vaccine creation or within seven days prior to vaccine administration (subjects on prophylactic agents are acceptable) * Subjects with any known life-threatening illness, medical condition, or organ system dysfunction (aside from their cancer), which in the investigator's opinion, could compromise subject safety * Subjects with known active hepatitis B virus or untreated hepatitis C virus, and, patients with previous history of hepatitis C who completed treatment for HCV are not excluded as long as they have no detectable viral load. * Subjects with known human immunodeficiency virus with CD4+T cells ≤ 350 cells/ul, a positive viral load as determined by institutional standard testing, or a known history of AIDS defining opportunistic infection within the last 12 months per subject medical records. * Known clinically relevant active autoimmune disease that would pose significant risk to the patient's life should a flare ensue. Patients with chronic autoimmune rheumatologic endocrine, or psoriatic skin diseases may still be eligible pending they are not receiving systemic immunosuppression at the time of treatment as previously described and that patients are aware of the increased risk of flare provocation with treatment. * Symptomatic congestive heart failure (NYHA Class 3 or 4) * Subjects with unstable angina pectoris * Known unstable cardiac arrythmias, abnormalities or transmural myocardial infarction within the last 6 months of treatment * Subjects who are post-splenectomy or otherwise asplenic * Personal history of anaphylactic reaction to previous vaccination * Known hypersensitivity to the active substance or to any of the excipients * Participants of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 months after the last dose of study treatment * Participants who are confirmed to be pregnant or breastfeeding * Known history of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician * Administration of a vaccine containing live virus within 30 days prior to the first dose of trial treatment. Note: Most flu vaccines are killed viruses, with the exception of the intra-nasal vainer (Flu-Mist) which is an attenuated live virus and therefore prohibited for 30 days prior to first dose. Non-live versions of the COVID vaccine are allowed. * Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness. * Subjects with sarcoma originating from bone or cartilage * Sarcomatous malignancies lacking metastatic potential i.e. well-differentiated liposarcoma, dermatofibrosarcoma protuberans, desmoid fibromatosis, etc.