Selectively altering microbiota for immune modulation

A method for enhancing efficacy of a therapy of a cancer in a human or animal patient, wherein the method comprises

• a. contacting a microbiota of the patient with an engineered nucleic acid sequence for producing a host modifying (HM) crRNA, and
• b. producing the HM-crRNA in a host cell of a target bacterial or archaeal sub-population of a microbiota,
• wherein the HM-crRNA is operable with a Cas nuclease in the host cell to form a HM-CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas system, and wherein the HM-crRNA comprises a sequence that is capable of hybridizing to a target sequence of the host cell to guide the Cas nuclease to the target sequence in the host cell, whereby the target sequence is modified by the HM-CRISPR/Cas system and the host cell is selectively killed or growth of the target sub-population is selectively reduced, thereby increasing the relative proportion of a sub-population of non-target bacteria in the microbiota, wherein the sub-population of non-target bacteria comprise Enterococcus,
• wherein the therapy comprises administration of an effective amount of an immune checkpoint inhibitor to the patient, wherein the immune checkpoint inhibitor is a PD-1 (Programmed Cell Death Protein 1) inhibitor or a PD-L1 (Programmed Death-Ligand 1) inhibitor, and
• wherein the increasing the relative proportion of the sub-population of the second bacterial species in the microbiota modulates immune cells in the patient, whereby the efficacy of the therapy is enhanced for treatment of the cancer in the patient.