• Frozen biopsy consistent with glioma by neuropathologist at the time of the first surgery in this longitudinal trial. Biopsy confirmation of glioma or infiltrative glioma at time of surgery will be acceptable, provided the subject has prior pathology confirmation of IDH wild-type glioma. Patients with reactive changes, gliosis or normal brain tissue only, without evidence of glioma at initial study surgery only will not receive study rQNestin34.5v.2 therapy and will be replaced. Confirmation of glioma at subsequent neurosurgical procedures beyond the initial surgery will not be required.

• Participants must have prior diagnosis of IDH wild-type glial tumor including GBM, grade 3 anaplastic astrocytoma or oligodendroglioma or or grade 2 astrocytoma with genetic features consistent with GBM, as confirmed by a neuropathologist or by a previous local pathology report. IDH wild-type designation may be based on negative immunohistochemistry (IDH1 R132H mutation) or next generation sequencing for patients with grade 4 tumor and by negative next-generation sequencing for those with grade 2 or 3 tumors. Patients with negative immunohistochemistry study for IDH1 R132H who are identified to have an alternative mutation of IDH1 or 2 are also not eligible.

• Prior history of external beam radiotherapy ≥ 5,000 cGy delivered to the tumor at least 4 weeks prior to OHRS registration. Participants over the age of 70 with prior history of hypofractionated external beam radiotherapy will also be accommodated, in accordance with NCCN guidelines.

• Prior history of temozolomide chemotherapy provided concurrent with external beam radiotherapy and after as per current standard of care. However, temozolomide is not required to have been provided concomitantly or after radiation if the patient had unmethylated MGMT promoter. At least 23 days must have passed from the last dose of temozolomide and first dose of rQNestin34.5v.2.

• For use of other investigational drug or other anti-tumor treatment, the following time periods must have elapsed from the projected start of scheduled study treatment: 4 weeks or 5 half-lives (whichever is shorter) from any investigational agent; 4 weeks from cytotoxic therapy (except 23 days for TMZ; 6 weeks from last dose for nitrosoureas); 12 weeks from completion of prior radiation therapy; 6 weeks from antibodies treatment; 4 weeks or 5 half-lives (whichever is shorter) from other anti-tumor therapies; 1 day from NOVO-TTF (Optune®) or prior cancer vaccine therapy

• The initial recurrent or residual gadolinium-enhancing lesion to be treated must be at least 1.0 cm in diameter and less than or equal to 2 cm in greatest maximal diameter, as determined by MRI. The initially treated lesion must be located in non-eloquent cortex, defined as non-dominant temporal, frontal, or occipital lobe. If located in the dominant cortex, the lesion must be in the occipital lobe. For lesions in dominant or non-dominant lobes, there should be a judgment that the subject will be able to tolerate multiple injections and biopsies, based on sufficient distance from the enhancing edge and eloquent cortex defined as speech (dominant mid-to posterior temporal lobe, parietal lobe and frontal lobe: Broca's area), memory (hippocampus and mesial dominant temporal lobe), or sensorimotor cortex. Subsequent injections (injections at day 15, 30, 60, 90, 120) will not be subject to the limitations of the initially treated lesion detailed above.

• Normal hematological, renal and liver function as defined below before first injection: ANC ≥ 1000/mcL, platelets ≥100,000/mcL, PT or PTT \<1.5 x institutional upper limit, Hemoglobin \>9.0 g/dL, Total serum bilirubin ≤ 1.5 upper normal institutional limits, AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal, and Serum creatinine ≤ 1.5 upper normal institutional limits OR Creatinine clearance ≥60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal.

• Karnofsky Performance Score ≥70.

• Age ≥ 18 years;

• Ability to understand and the willingness to sign a written informed consent document;

• The effects of rQNestin34.5v.2 and cyclophosphamide on the developing human fetus are unknown. For this reason and because cytotoxic \& immunomodulating 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 including 3 months following the study. 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of study participation including 3 months following the study. Women of child-bearing potential must have a negative serum pregnancy test within 48 hours of study registration.

• No dexamethasone therapy for at least 14 days prior to the first rQNestin34.5v.2 inoculation. Patients who are on physiologic doses of corticosteroids for the treatment of adrenal insufficiency will be allowed to enroll.

• Ability to undergo MRI scanning with contrast;

• Have residual tumor or be at first or second relapse. Note: Relapse is defined as progression following initial therapy (i.e., radiation ± chemotherapy). For participants who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse. Residual tumor is defined as contrast-enhancing tumor that is present after the initial surgery, radiation, and chemotherapy.

• Participants must have recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy (exceptions include but not limited to alopecia, laboratory values not listed per inclusion criteria, and lymphopenia which is common after therapy with temozolomide).