The goal of this clinical trial is to learn if DOC1021 + pIFN alongside standard of care (SOC) will improve survival in adult patients newly diagnosed with glioblastoma (IDH-wt). It will also evaluate the safety of DOC1021 + pIFN. Researchers will compare DOC1021 dendritic cell immunotherapy regimen added to SOC compared to SOC treatment alone.

Participants in the DOC1021 + pIFN + SOC arm will:

• Take filgrastim subcutaneously x 5 doses and subsequently undergo a leukapheresis collection
• Undergo ultrasound guided perinodal DOC1021 injections every 2 weeks for a total of 3 doses
• Receive subcutaneous pIFN injections weekly for a total of 6 doses in parallel with the DOC1021 injections

Both arms of the trial will:

- Visit the clinic regularly to assess quality of life, symptoms, medication use, imaging, bloodwork, and to receive SOC treatment with surgery, temozolomide chemotherapy and radiation

Inclusion Criteria:

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Age 18 years or older

4. Presumed diagnosis of glioblastoma IDH-wt (as per the 2021 WHO Classification of CNS Tumors) deemed to be potentially resectable and deemed to be a good candidate for post-operative standard of care temozolomide and radiation therapy.

   1. Surgical objective is for gross total resection (GTR)/near-total resection (NTR) de-fined as ≥ 95% of contrast enhancing (CE) tumor removed plus ≤ 1 cm3 residual CE tumor. Patients with subtotal resection will still be eligible if at least 70% of the CE tumor is resected.
   2. Eligibility will be confirmed after surgery when diagnosis of glioblastoma IDH-wt confirmed prior to randomization. Randomization can occur with only IDH1 immunohistochemistry and when additional molecular testing is available, if glioblastoma IDH-wt is not confirmed, the participant will be deemed a screen failure and replaced.
   3. Patients with prior biopsy or subtotal resection are eligible if no other anti-cancer treatment received for glioblastoma and additional resection indicated.

5. Ability to receive filgrastim (e.g., Neupogen), leukapheresis and 3 bi-weekly injections of DOC1021 near deep cervical lymph nodes + weekly pIFN x 6 weeks.

6. Females of reproductive potential must have a negative serum pregnancy test and agree to use effective contraception (as determined appropriate for the patient by the investigator) during study treatment.

7. Adequate kidney, liver, bone marrow function, and immune function, as follows:

   1. Hemoglobin ≥ 8.0 gm/dL
   2. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
   3. Platelet count ≥ 75,000/mm3
   4. Calculated creatinine clearance (CrCl) > 30 mL/min using Cockcroft and Gault for-mula:

   i. For males = (140 - age[years]) x (body weight [kg]) / (72 x serum creatinine [mg/dL]) ii. For females = 0.85 x value from male formula e. Total bilirubin ≤ 1.5 times upper limit of normal (ULN) except in patients with Gilbert's disease for which total bilirubin must be ≤ 2 times ULN f. Aspartate transaminase AST (SGOT) and alanine aminotransferase ALT (SGPT) ≤ 3 times the ULN

8. Karnofsky Performance Score ≥ 70

Exclusion Criteria:

1. Infratentorial, recurrent, leptomeningeal or extracranial disease.
2. Patients who are pregnant or breastfeeding.
3. Known active HIV or hepatitis infection. Patients with HIV that is well-controlled and have undetectable viral titers remain eligible. Patients with history of HCV adequately treated such that RNA viral load is negative also remain eligible.
4. Any severe or uncontrolled medical condition or other condition that could affect participation in this study as determined by the investigator, including but not limited to: uncontrolled or severe cardiac disease, systemic autoimmune disorders requiring immunosuppression in the past 2 years*, autoimmune hyper/hypothyroidism, untreated viral hepatitis, autoimmune hepatitis. *autoimmune disorders include but are not limited to rheumatoid arthritis, psoriasis and inflammatory bowel disease and immunosuppressive medications include DMARDs like methotrexate, TNF inhibitors, IL-6 receptor blockers, CD80/86 inhibitors, anti-CD20 and JAK inhibitors
5. Treatment with another investigational drug or other experimental intervention within the last 30 days.